公开(公告)号：EP3336550A1

公开(公告)日：2018-06-20

申请号：EP17202931.6

申请日：2008-09-10

申请人： Universiteit Leiden ,  Academisch Ziekenhuis Leiden Acting Under The Name Leiden University Medical Center

发明人： BIESSEN, Ericus Anna Leonardus ,  VAN BERKEL, Theodorus Josephus Cornelis ,  KRAAIJEVELD, Adriaan Otto

IPC分类号： G01N33/68 ,  A61P9/00

摘要： The present invention relates to the identification of chemokine biomarkers predictive of future acute coronary syndromes including unstable angina pectoris (UAP). The present invention also identifies particular chemokines as potential therapeutic targets for intervention in cardiovascular diseases.

公开(公告)号：EP3262170A1

公开(公告)日：2018-01-03

申请号：EP16707414.5

申请日：2016-02-26

申请人： ProQR Therapeutics II B.V.

发明人： BIASUTTO, Patricia Coromoto ,  CHAN, Hee, Lam

IPC分类号： C12N15/113 ,  A61K31/712 ,  A61K31/7125

CPC分类号： C12N15/113 ,  A61K31/7125 ,  C12N2310/11 ,  C12N2310/315 ,  C12N2310/346 ,  C12N2320/33 ,  C12N2330/51 ,  C12N2310/321 ,  C12N2310/3521

摘要： Antisense oligonucleotides target the mutation in intron 26 of the CEP290 gene and reduce inclusion of the aberrant exon into the CEP290 mRNA. The oligonucleotides include no more than 3 consecutive guanosines, have no more than 60% guanosine nucleobases, include at most one CpG sequence, and/or do not have the potential to form a hairpin comprising 3 or more consecutive complementary base pairs.

公开(公告)号：EP3138912A1

公开(公告)日：2017-03-08

申请号：EP16183725.7

申请日：2013-12-05

申请人： Sigma-Aldrich Co. LLC

发明人： Chen, Fuqiang ,  Davis, Gregory D. ,  Kang, Qiaohua ,  Knight, Scott W.

IPC分类号： C12N15/10 ,  C12N15/63 ,  C12N9/22

CPC分类号： C12N15/907 ,  A61K38/00 ,  C07K7/06 ,  C07K14/463 ,  C07K2319/09 ,  C07K2319/10 ,  C07K2319/81 ,  C12N7/00 ,  C12N9/22 ,  C12N9/96 ,  C12N15/102 ,  C12N15/11 ,  C12N15/63 ,  C12N15/67 ,  C12N15/85 ,  C12N15/86 ,  C12N2310/3513 ,  C12N2750/14143 ,  C12N2800/22 ,  C12N2800/80 ,  C12Y301/00 ,  C12Y301/21004

摘要： The present invention provides RNA-guided endonucleases, which are engineered for expression in eukaryotic cells or embryos, and methods of using the RNA-guided endonuclease for targeted genome modification in in eukaryotic cells or embryos. Also provided are fusion proteins, wherein each fusion protein comprises a CRISPR/Cas-like protein or fragment thereof and an effector domain. The effector domain can be a cleavage domain, an epigenetic modification domain, a transcriptional activation domain, or a transcriptional repressor domain. Also provided are methods for using the fusion proteins to modify a chromosomal sequence or regulate expression of a chromosomal sequence.

公开(公告)号：EP3138910A1

公开(公告)日：2017-03-08

申请号：EP16183723.2

申请日：2013-12-05

申请人： Sigma-Aldrich Co. LLC

发明人： Chen, Fuqiang ,  Davis, Gregory D. ,  Kang, Qiaohua ,  Knight, Scott W.

IPC分类号： C12N15/10 ,  C12N15/63 ,  C12N9/22

CPC分类号： C12N15/907 ,  A61K38/00 ,  C07K7/06 ,  C07K14/463 ,  C07K2319/09 ,  C07K2319/10 ,  C07K2319/81 ,  C12N7/00 ,  C12N9/22 ,  C12N9/96 ,  C12N15/102 ,  C12N15/11 ,  C12N15/63 ,  C12N15/67 ,  C12N15/85 ,  C12N15/86 ,  C12N2310/3513 ,  C12N2750/14143 ,  C12N2800/22 ,  C12N2800/80 ,  C12Y301/00 ,  C12Y301/21004

摘要： The present invention provides RNA-guided endonucleases, which are engineered for expression in eukaryotic cells or embryos, and methods of using the RNA-guided endonuclease for targeted genome modification in in eukaryotic cells or embryos. Also provided are fusion proteins, wherein each fusion protein comprises a CRISPR/Cas-like protein or fragment thereof and an effector domain. The effector domain can be a cleavage domain, an epigenetic modification domain, a transcriptional activation domain, or a transcriptional repressor domain. Also provided are methods for using the fusion proteins to modify a chromosomal sequence or regulate expression of a chromosomal sequence.

公开(公告)号：EP3138909A1

公开(公告)日：2017-03-08

申请号：EP16183717.4

申请日：2013-12-05

申请人： Sigma-Aldrich Co. LLC

发明人： Chen, Fuqiang ,  Davis, Gregory D. ,  Kang, Qiaohua ,  Knight, Scott W.

IPC分类号： C12N15/10 ,  C12N15/63 ,  C12N9/22

CPC分类号： C12N15/907 ,  A61K38/00 ,  C07K7/06 ,  C07K14/463 ,  C07K2319/09 ,  C07K2319/10 ,  C07K2319/81 ,  C12N7/00 ,  C12N9/22 ,  C12N9/96 ,  C12N15/102 ,  C12N15/11 ,  C12N15/63 ,  C12N15/67 ,  C12N15/85 ,  C12N15/86 ,  C12N2310/3513 ,  C12N2750/14143 ,  C12N2800/22 ,  C12N2800/80 ,  C12Y301/00 ,  C12Y301/21004

摘要： The present invention provides RNA-guided endonucleases, which are engineered for expression in eukaryotic cells or embryos, and methods of using the RNA-guided endonuclease for targeted genome modification in in eukaryotic cells or embryos. Also provided are fusion proteins, wherein each fusion protein comprises a CRISPR/Cas-like protein or fragment thereof and an effector domain. The effector domain can be a cleavage domain, an epigenetic modification domain, a transcriptional activation domain, or a transcriptional repressor domain. Also provided are methods for using the fusion proteins to modify a chromosomal sequence or regulate expression of a chromosomal sequence.

摘要翻译： 本发明提供了用于在真核细胞或胚胎中表达的RNA引导的内切核酸酶，以及使用RNA引导的内切核酸酶在真核细胞或胚胎中靶向基因组修饰的方法。 还提供了融合蛋白，其中每个融合蛋白包含CRISPR / Cas样蛋白或其片段和效应结构域。 效应结构域可以是切割结构域，表观遗传修饰结构域，转录激活结构域或转录阻遏物结构域。 还提供了使用融合蛋白修饰染色体序列或调节染色体序列表达的方法。

公开(公告)号：EP3137633A1

公开(公告)日：2017-03-08

申请号：EP15786641.9

申请日：2015-04-24

申请人： Sigma-Aldrich Co. LLC

发明人： DAVIS, Gregory D. ,  KANG, Qiaohua

IPC分类号： C12Q1/68 ,  C12Q1/02

CPC分类号： C12Q1/6883 ,  C12N15/907 ,  C12N2510/00 ,  C12Q1/6886 ,  C12Q2600/118 ,  C12Q2600/154 ,  C12Q2600/166

摘要： The present disclosure provides genetically engineered cell lines comprising chromosomally integrated synthetic sequences having predetermined epigenetic modifications, wherein a predetermined epigenetic modification is correlated with a known diagnosis, prognosis or level of sensitivity to a disease treatment. Also provided are kits comprising said epigenetically modified synthetic nucleic acids or cells comprising said epigenetically modified synthetic nucleic acids that can be used as reference standards for predicting responsiveness to therapeutic treatments, diagnosing diseases, or predicting disease prognosis.

摘要翻译： 本公开提供了包含具有预定表观遗传修饰的染色体整合的合成序列的遗传工程改造的细胞系，其中预定的表观遗传修饰与已知的疾病治疗的敏感性的诊断，预后或水平相关。 还提供了包含所述表观遗传修饰的合成核酸或包含所述表观遗传修饰的合成核酸的细胞的试剂盒，其可以用作预测对治疗性治疗的响应性，诊断疾病或预测疾病预后的参考标准。

公开(公告)号：EP3104849A1

公开(公告)日：2016-12-21

申请号：EP15748750.5

申请日：2015-02-13

申请人： The Board of Trustees of the University of Arkansas ,  Arkansas Children's Hospital Research Institute, Inc.

发明人： JAMES, Laura P. ,  HINSON, Jack ,  ROBERTS, Dean ,  GILL, Pritmohinder S.

IPC分类号： A61K31/167

CPC分类号： C12Q1/48 ,  C07K14/4708 ,  C12N9/1007 ,  C12N9/1014 ,  C12N9/107 ,  C12N9/1096 ,  C12Q1/527 ,  C12Y201/01005 ,  G01N33/53

摘要： The present disclosure relates to acetaminophen protein adducts and methods of diagnosing acetaminophen toxicity using the acetaminophen protein adducts. The present disclosure provides acetaminophen (APAP)-protein adducts and methods of detecting acetaminophen-induced toxicity in a subject using APAP-protein adducts. One aspect of the present disclosure provides an APAP-protein adduct for diagnosing acetaminophen-induced toxicity. According to the present disclosure, the inventors have identified proteins that are modified by N-acetyl-pbenzoquinoneimine (NAPQI) in subjects with acetaminophen-induced toxicity. Non-limiting examples of proteins modified by NAPQI include betaine-homocysteine S-methyltransferase 1, cytoplasmic aspartate aminotransferase, 1,4-alpha-glucan branching enzyme, formimidoyltransferase-cyclodeaminase, and dystrophin.

摘要翻译： 本公开涉及对乙酰氨基酚蛋白加合物和使用对乙酰氨基酚蛋白加合物诊断对乙酰氨基酚毒性的方法。 本公开提供使用APAP-蛋白质加合物的对象中对乙酰氨基酚（APAP） - 蛋白质加合物和检测对乙酰氨基酚诱导的毒性的方法。 本公开的一个方面提供了用于诊断对乙酰氨基酚诱导的毒性的APAP-促胰岛素加合物。 根据本公开内容，发明人已经鉴定了在具有对乙酰氨基酚诱导毒性的受试者中被N-乙酰基 - 苯醌亚胺（NAPQI）修饰的蛋白质。 NAPQI修饰的蛋白质的非限制性例子包括甜菜碱 - 高半胱氨酸S-甲基转移酶1，细胞质天冬氨酸转氨酶，1,4-α-葡聚糖分支酶，亚胺酰基转移酶 - 环化脱氨酶和肌营养不良蛋白。

公开(公告)号：EP3094719A2

公开(公告)日：2016-11-23

申请号：EP15737664.1

申请日：2015-01-14

申请人： COLORADO STATE UNIVERSITY RESEARCH FOUNDATION

发明人： KHETANI, Salman R. ,  BERGER, Dustin R. ,  WARE, Brenton R.

IPC分类号： C12N5/07

CPC分类号： C12N5/067 ,  C12N2501/237 ,  C12N2501/39 ,  C12N2502/13 ,  C12N2503/02 ,  C12N2533/90

摘要： The present disclosure provides co-cultures of human pluripotent stem cell derived hepatocytes and at least one non-parenchymal cell population in vitro, methods of preparing the co-cultures and methods of using the co-cultures for high throughput screening and evaluation of drug candidates. The stem cell derived hepatocyte co-culture system provides an in vitro model in which cell viability and relatively mature hepatocyte phenotype of stem cell derived hepatocytes are maintained for extended periods relative to conventional monoculture.

公开(公告)号：EP3080609A1

公开(公告)日：2016-10-19

申请号：EP14830849.7

申请日：2014-12-12

申请人： Electrophoretics Limited ,  King's College London

发明人： WARD, Malcolm Andrew ,  HYE, Abdul ,  LOVESTONE, Simon Harold ,  DOBSON, Richard James Butler

IPC分类号： G01N33/68

CPC分类号： G01N33/6896 ,  G01N2800/2814 ,  G01N2800/2821 ,  G01N2800/52

摘要： Alzheimer's disease, the most common cause of dementia in older individuals, is a debilitating neurodegenerative disease for which there is currently no cure. In the past, AD could only be definitively diagnosed by brain biopsy or upon autopsy after a patient died. These methods, which demonstrate the presence of the characteristic plaque and tangle lesions in the brain, are still considered the gold standard for the pathological diagnoses of AD. However, in the clinical setting brain biopsy is rarely performed and diagnosis depends on a battery of neurological, psychometric and biochemical tests, including the measurement of biochemical markers such as the ApoE and tau proteins or the beta-amyloid peptide in cerebrospinal fluid and blood. The present invention discloses and describes panels of makers that are differentially expressed in the disease state relative to their expression in the normal state and, in particular, identifies and describes panels of makers associated with neurocognitive disorders. Such biomarker panel might have considerable value in triaging patients with early memory disorders to yet more specific but more invasive and costly approaches such as molecular markers in CSF and on PET imaging in clinical trials and possibly in clinical practice.

公开(公告)号：EP3044250A1

公开(公告)日：2016-07-20

申请号：EP14843476.4

申请日：2014-09-10

申请人： COLORADO STATE UNIVERSITY RESEARCH FOUNDATION

发明人： JAMES, Susan P. ,  BAILEY, Travis S. ,  POPAT, Ketul C. ,  PRAWEL, David A. ,  LEWIS, Jackson T. ,  KOCH, Richard L.

IPC分类号： C08G77/20 ,  C08L43/04 ,  C08G63/91

CPC分类号： C08L43/04 ,  A61F2/16 ,  A61F2002/1681 ,  A61L27/48 ,  C08G77/388 ,  G02B1/043 ,  G02C7/049

摘要： Provided herein is a polymeric material comprising a polymer host; and a guest molecule comprising a glycosaminoglycan; wherein the guest molecule is disposed within the polymer host, and wherein the guest molecule is covalently bonded to at least one other guest molecule. In some embodiments, the polymer host comprises a silicone-based polymer. In other embodiments, the glycosaminoglycan is chosen from hyaluronic acid and derivatives thereof.