Pub Date : 2024-05-01Epub Date: 2024-06-17DOI: 10.1080/13543776.2024.2364798
Rosa Maria Vitale, Luciano de Petrocellis, Pietro Amodeo
Introduction: TRPA1 is a nonselective calcium channel, a member of the transient receptor potential (TRP) superfamily, also referred to as the 'irritant' receptor, being activated by pungent and noxious exogenous chemicals as well as by endogenous algogenic stimuli, to elicit pain, itching, and inflammatory conditions. For this reason, it is considered an attractive therapeutic target to treat a wide range of diseases including acute and chronic pain, itching, and inflammatory airway diseases.
Areas covered: The present review covers patents on TRPA1 antagonists disclosed from 2020 to present, falling in the following main classes: i) novel therapeutic applications for known or already disclosed antagonists, ii) identification and characterization of TRPA1 antagonists from natural sources, and iii) synthesis and evaluation of novel compounds.
Expert opinion: Despite the limited number of TRPA1 antagonists in clinical trials, there is an ever-growing interest on this receptor-channel as therapeutic target, mainly due to the relevant outcomes from basic research, which unveiled novel physio-pathological mechanisms where TRPA1 is believed to play a pivotal role, for example the Alzheimer's disease or ocular diseases, expanding the panel of potential therapeutic applications for TRPA1 modulators.
{"title":"An updated patent review of TRPA1 antagonists (2020 - present).","authors":"Rosa Maria Vitale, Luciano de Petrocellis, Pietro Amodeo","doi":"10.1080/13543776.2024.2364798","DOIUrl":"10.1080/13543776.2024.2364798","url":null,"abstract":"<p><strong>Introduction: </strong>TRPA1 is a nonselective calcium channel, a member of the transient receptor potential (TRP) superfamily, also referred to as the 'irritant' receptor, being activated by pungent and noxious exogenous chemicals as well as by endogenous algogenic stimuli, to elicit pain, itching, and inflammatory conditions. For this reason, it is considered an attractive therapeutic target to treat a wide range of diseases including acute and chronic pain, itching, and inflammatory airway diseases.</p><p><strong>Areas covered: </strong>The present review covers patents on TRPA1 antagonists disclosed from 2020 to present, falling in the following main classes: i) novel therapeutic applications for known or already disclosed antagonists, ii) identification and characterization of TRPA1 antagonists from natural sources, and iii) synthesis and evaluation of novel compounds.</p><p><strong>Expert opinion: </strong>Despite the limited number of TRPA1 antagonists in clinical trials, there is an ever-growing interest on this receptor-channel as therapeutic target, mainly due to the relevant outcomes from basic research, which unveiled novel physio-pathological mechanisms where TRPA1 is believed to play a pivotal role, for example the Alzheimer's disease or ocular diseases, expanding the panel of potential therapeutic applications for TRPA1 modulators.</p>","PeriodicalId":12314,"journal":{"name":"Expert Opinion on Therapeutic Patents","volume":" ","pages":"315-332"},"PeriodicalIF":5.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141283388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: PIM Kinases (PIM-1, PIM-2, and PIM-3) have been reported to play crucial role in signaling cascades that govern cell survival, proliferation, and differentiation. Over-expression of these kinases leads to hematological malignancies such as diffuse large B cell lymphomas (DLBCL), multiple myeloma, leukemia, lymphoma and prostate cancer etc. PIM kinases as biomarkers and potential therapeutic targets have shown promise toward precision cancer therapy. The selective PIM-1, PIM-2, and/or PIM-3 isoform inhibitors have shown significant results in patients with advanced stages of cancer including relapsed/refractory cancer.
Areas covered: A comprehensive literature review of PIM Kinases (PIM-1, PIM-2, and PIM-3) in oncogenesis, the patented PIM kinase inhibitors (2016-Present), and their pharmacological and structural insights have been highlighted.
Expert opinion: Recently, PIM kinases viz. PIM-1, PIM-2, and PIM-3 (members of the serine/threonine protein kinase family) as therapeutic targets have attracted considerable interest in oncology especially in hematological malignancies. The patented PIM kinase inhibitors comprised of heterocyclic (fused)ring structure(s) like indole, pyridine, pyrazine, pyrazole, pyridazine, piperazine, thiazole, oxadiazole, quinoline, triazolo-pyridine, pyrazolo-pyridine, imidazo-pyridazine, oxadiazole-thione, pyrazolo-pyrimidine, triazolo-pyridazine, imidazo-pyridazine, pyrazolo-quinazoline and pyrazolo-pyridine etc. showed promising results in cancer chemotherapy.
{"title":"PIM kinase inhibitors: an updated patent review (2016-present).","authors":"Anushka Sharma, Rahul Dubey, Shankar Gupta, Vivek Asati, Vipul Kumar, Dileep Kumar, Debarshi Kar Mahapatra, Meenakshi Jaiswal, Sanmati Kumar Jain, Sanjay Kumar Bharti","doi":"10.1080/13543776.2024.2365411","DOIUrl":"10.1080/13543776.2024.2365411","url":null,"abstract":"<p><strong>Introduction: </strong>PIM Kinases (PIM-1, PIM-2, and PIM-3) have been reported to play crucial role in signaling cascades that govern cell survival, proliferation, and differentiation. Over-expression of these kinases leads to hematological malignancies such as diffuse large B cell lymphomas (DLBCL), multiple myeloma, leukemia, lymphoma and prostate cancer etc. PIM kinases as biomarkers and potential therapeutic targets have shown promise toward precision cancer therapy. The selective PIM-1, PIM-2, and/or PIM-3 isoform inhibitors have shown significant results in patients with advanced stages of cancer including relapsed/refractory cancer.</p><p><strong>Areas covered: </strong>A comprehensive literature review of PIM Kinases (PIM-1, PIM-2, and PIM-3) in oncogenesis, the patented PIM kinase inhibitors (2016-Present), and their pharmacological and structural insights have been highlighted.</p><p><strong>Expert opinion: </strong>Recently, PIM kinases viz. PIM-1, PIM-2, and PIM-3 (members of the serine/threonine protein kinase family) as therapeutic targets have attracted considerable interest in oncology especially in hematological malignancies. The patented PIM kinase inhibitors comprised of heterocyclic (fused)ring structure(s) like indole, pyridine, pyrazine, pyrazole, pyridazine, piperazine, thiazole, oxadiazole, quinoline, triazolo-pyridine, pyrazolo-pyridine, imidazo-pyridazine, oxadiazole-thione, pyrazolo-pyrimidine, triazolo-pyridazine, imidazo-pyridazine, pyrazolo-quinazoline and pyrazolo-pyridine etc. showed promising results in cancer chemotherapy.</p>","PeriodicalId":12314,"journal":{"name":"Expert Opinion on Therapeutic Patents","volume":" ","pages":"365-382"},"PeriodicalIF":5.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141261381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-01Epub Date: 2024-06-13DOI: 10.1080/13543776.2024.2365410
Alessia Petrocchi, Alina Ciammaichella
Introduction: SHP2 (Src homology region 2-containing protein tyrosine phosphatase 2) is a target of interest for cancer therapy due to its key role in the regulation of the RAS/MAPK signal transduction pathway downstream of Receptor Tyrosine Kinases (RTKs). Moreover, SHP2 can inhibit T cells via the PD-1/PD-L1 pathway. SHP2 plays a critical role in numerous physiological and pathological cellular processes, such as cell proliferation, survival, and migration.
Areas covered: This review examines SHP2 allosteric inhibitors reported in patents published in Espacenet and Scifinder databases from 2018 to present. An overview of claimed structures is conducted, focusing attention on structural modifications compared to SHP099, the first described allosteric inhibitor of SHP2.
Expert opinion: Multiple potent allosteric SHP2 inhibitors have been discovered, disclosed, and tested in a variety of preclinical cancer models with strong evidence of efficacy. Fifteen compounds are currently in clinical development, but none of them have been approved for marketing. Until now, long-term benefit of SHP2 inhibitors as monotherapy agents have not been demonstrated due to acquired mechanisms of resistance and/or lack of efficacy. However, combination therapies with a variety of agents, such as MEK, BRAF, EGFR, RAS-G12C and PDL-1 inhibitors, have high potential and are currently an extensive area of investigation.
{"title":"A patent review of SHP2 allosteric inhibitors (2018-present).","authors":"Alessia Petrocchi, Alina Ciammaichella","doi":"10.1080/13543776.2024.2365410","DOIUrl":"10.1080/13543776.2024.2365410","url":null,"abstract":"<p><strong>Introduction: </strong>SHP2 (Src homology region 2-containing protein tyrosine phosphatase 2) is a target of interest for cancer therapy due to its key role in the regulation of the RAS/MAPK signal transduction pathway downstream of Receptor Tyrosine Kinases (RTKs). Moreover, SHP2 can inhibit T cells via the PD-1/PD-L1 pathway. SHP2 plays a critical role in numerous physiological and pathological cellular processes, such as cell proliferation, survival, and migration.</p><p><strong>Areas covered: </strong>This review examines SHP2 allosteric inhibitors reported in patents published in Espacenet and Scifinder databases from 2018 to present. An overview of claimed structures is conducted, focusing attention on structural modifications compared to SHP099, the first described allosteric inhibitor of SHP2.</p><p><strong>Expert opinion: </strong>Multiple potent allosteric SHP2 inhibitors have been discovered, disclosed, and tested in a variety of preclinical cancer models with strong evidence of efficacy. Fifteen compounds are currently in clinical development, but none of them have been approved for marketing. Until now, long-term benefit of SHP2 inhibitors as monotherapy agents have not been demonstrated due to acquired mechanisms of resistance and/or lack of efficacy. However, combination therapies with a variety of agents, such as MEK, BRAF, EGFR, RAS-G12C and PDL-1 inhibitors, have high potential and are currently an extensive area of investigation.</p>","PeriodicalId":12314,"journal":{"name":"Expert Opinion on Therapeutic Patents","volume":" ","pages":"383-396"},"PeriodicalIF":5.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141261295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-01Epub Date: 2024-06-11DOI: 10.1080/13543776.2024.2365407
Clemente Capasso, Claudiu T Supuran
Introduction: This review offers an updated perspective on the biomedical applications of prokaryotic carbonic anhydrases (CAs), emphasizing their potential as targets for drug development against antibiotic-resistant bacterial infections. A systematic review of literature from PubMed, Web of Science, and Google Scholar has been conducted to provide a comprehensive analysis.
Area covered: It delves into the pivotal roles of prokaryotic CAs in bacterial metabolism and their distinctions from mammalian CAs. The review explores the diversity of CA classes in bacteria, discusses selective inhibitors targeting bacterial CAs, and explores their potential applications in biomedical research. Furthermore, it analyzes clinical trials investigating the efficacy of carbonic anhydrase inhibitors (CAIs) and patented approaches for developing antibacterial CAIs, highlighting their translational potential in creating innovative antibacterial agents.
Expert opinion: Recent years have witnessed increased recognition of CA inhibition as a promising strategy against bacterial infections. Challenges persist in achieving selectivity over human isoforms and optimizing therapeutic efficacy. Structural biology techniques provide insights into unique active site architectures, guiding selective inhibitor design. The review underscores the importance of interdisciplinary collaborations, innovative drug delivery systems, and advanced drug discovery approaches in unlocking the full therapeutic potential of prokaryotic CA inhibitors. It emphasizes the significance of these efforts in addressing antibiotic resistance and improving patient outcomes.
导言:这篇综述提供了原核生物碳酸酐酶(CAs)生物医学应用的最新视角,强调了它们作为抗生素耐药细菌感染药物开发靶点的潜力。为了提供全面的分析,我们对来自 PubMed、Web of Science 和 Google Scholar 的文献进行了系统综述:该综述深入探讨了原核 CA 在细菌新陈代谢中的关键作用及其与哺乳动物 CA 的区别。综述探讨了细菌中 CA 种类的多样性,讨论了针对细菌 CA 的选择性抑制剂,并探讨了它们在生物医学研究中的潜在应用。此外,它还分析了研究碳酸酐酶抑制剂(CAIs)疗效的临床试验以及开发抗菌 CAIs 的专利方法,强调了它们在创造创新抗菌剂方面的转化潜力:近年来,人们越来越认识到CA抑制剂是一种很有前景的抗细菌感染策略。在实现对人类同工酶的选择性和优化疗效方面,挑战依然存在。结构生物学技术提供了对独特活性位点结构的见解,为选择性抑制剂的设计提供了指导。这篇综述强调了跨学科合作、创新给药系统和先进药物发现方法在充分挖掘原核 CA 抑制剂治疗潜力方面的重要性。它强调了这些努力在解决抗生素耐药性和改善患者预后方面的重要意义。
{"title":"Biomedical applications of prokaryotic carbonic anhydrases: an update.","authors":"Clemente Capasso, Claudiu T Supuran","doi":"10.1080/13543776.2024.2365407","DOIUrl":"10.1080/13543776.2024.2365407","url":null,"abstract":"<p><strong>Introduction: </strong>This review offers an updated perspective on the biomedical applications of prokaryotic carbonic anhydrases (CAs), emphasizing their potential as targets for drug development against antibiotic-resistant bacterial infections. A systematic review of literature from PubMed, Web of Science, and Google Scholar has been conducted to provide a comprehensive analysis.</p><p><strong>Area covered: </strong>It delves into the pivotal roles of prokaryotic CAs in bacterial metabolism and their distinctions from mammalian CAs. The review explores the diversity of CA classes in bacteria, discusses selective inhibitors targeting bacterial CAs, and explores their potential applications in biomedical research. Furthermore, it analyzes clinical trials investigating the efficacy of carbonic anhydrase inhibitors (CAIs) and patented approaches for developing antibacterial CAIs, highlighting their translational potential in creating innovative antibacterial agents.</p><p><strong>Expert opinion: </strong>Recent years have witnessed increased recognition of CA inhibition as a promising strategy against bacterial infections. Challenges persist in achieving selectivity over human isoforms and optimizing therapeutic efficacy. Structural biology techniques provide insights into unique active site architectures, guiding selective inhibitor design. The review underscores the importance of interdisciplinary collaborations, innovative drug delivery systems, and advanced drug discovery approaches in unlocking the full therapeutic potential of prokaryotic CA inhibitors. It emphasizes the significance of these efforts in addressing antibiotic resistance and improving patient outcomes.</p>","PeriodicalId":12314,"journal":{"name":"Expert Opinion on Therapeutic Patents","volume":" ","pages":"351-363"},"PeriodicalIF":5.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141261418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-22DOI: 10.1080/13543776.2024.2346325
Wenhao Guo, Hanwen Liu, Yong Yan, Di Wu, Hequan Yao, Kejiang Lin, Xuanyi Li
The TGF-β signaling pathway is a complex network that plays a crucial role in regulating essential biological functions and is implicated in the onset and progression of multiple diseases. This rev...
{"title":"Targeting the TGF-β signaling pathway: an updated patent review (2021–present)","authors":"Wenhao Guo, Hanwen Liu, Yong Yan, Di Wu, Hequan Yao, Kejiang Lin, Xuanyi Li","doi":"10.1080/13543776.2024.2346325","DOIUrl":"https://doi.org/10.1080/13543776.2024.2346325","url":null,"abstract":"The TGF-β signaling pathway is a complex network that plays a crucial role in regulating essential biological functions and is implicated in the onset and progression of multiple diseases. This rev...","PeriodicalId":12314,"journal":{"name":"Expert Opinion on Therapeutic Patents","volume":"18 1","pages":""},"PeriodicalIF":6.6,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140636897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-08DOI: 10.1080/13543776.2024.2340569
Enrico Mario Alessandro Fassi, Andrea Citarella, Marco Albani, Erica Ginevra Milano, Laura Legnani, Carmen Lammi, Alessandra Silvani, Giovanni Grazioso
Published in Expert Opinion on Therapeutic Patents (Just accepted, 2024)
发表于《关于治疗专利的专家意见》(刚刚接受,2024 年)
{"title":"PCSK9 inhibitors: a patent review 2018-2023","authors":"Enrico Mario Alessandro Fassi, Andrea Citarella, Marco Albani, Erica Ginevra Milano, Laura Legnani, Carmen Lammi, Alessandra Silvani, Giovanni Grazioso","doi":"10.1080/13543776.2024.2340569","DOIUrl":"https://doi.org/10.1080/13543776.2024.2340569","url":null,"abstract":"Published in Expert Opinion on Therapeutic Patents (Just accepted, 2024)","PeriodicalId":12314,"journal":{"name":"Expert Opinion on Therapeutic Patents","volume":"106 1","pages":""},"PeriodicalIF":6.6,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140571068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-05DOI: 10.1080/13543776.2024.2338101
Valentina Puca, Beatrice Marinacci, Benedetta Pellegrini, Floriana Campanile, Maria Santagati, Rossella Grande
Bacterial Membrane Vesicles (MVs) play important roles in cell-to-cell communication and transport of several molecules. Such structures are essential components of Extracellular Polymeric Substanc...
{"title":"Biofilm and bacterial membrane vesicles: recent advances","authors":"Valentina Puca, Beatrice Marinacci, Benedetta Pellegrini, Floriana Campanile, Maria Santagati, Rossella Grande","doi":"10.1080/13543776.2024.2338101","DOIUrl":"https://doi.org/10.1080/13543776.2024.2338101","url":null,"abstract":"Bacterial Membrane Vesicles (MVs) play important roles in cell-to-cell communication and transport of several molecules. Such structures are essential components of Extracellular Polymeric Substanc...","PeriodicalId":12314,"journal":{"name":"Expert Opinion on Therapeutic Patents","volume":"5 1","pages":""},"PeriodicalIF":6.6,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140571165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-05DOI: 10.1080/13543776.2024.2338111
Kyle D. Reichl, Esther C. Y. Lee, Ariamala Gopalsamy
The multi-subunit SWI/SNF chromatin remodeling complex is a key epigenetic regulator for many cellular processes, and several subunits are found to be mutated in human cancers. The inactivating mut...
{"title":"Synthetic lethality: targeting SMARCA2 ATPase in SMARCA4-deficient tumors – a review of patent literature from 2019–30 June 2023","authors":"Kyle D. Reichl, Esther C. Y. Lee, Ariamala Gopalsamy","doi":"10.1080/13543776.2024.2338111","DOIUrl":"https://doi.org/10.1080/13543776.2024.2338111","url":null,"abstract":"The multi-subunit SWI/SNF chromatin remodeling complex is a key epigenetic regulator for many cellular processes, and several subunits are found to be mutated in human cancers. The inactivating mut...","PeriodicalId":12314,"journal":{"name":"Expert Opinion on Therapeutic Patents","volume":"5 1","pages":""},"PeriodicalIF":6.6,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140571075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-04DOI: 10.1080/13543776.2024.2338099
Md Toufiqur Rahman, Hetti Handi Chaminda Lakmal, Javeena Hussain, Chunyang Jin
The neuropeptide relaxin-3/RXFP3 system belongs to the relaxin/insulin superfamily and is involved in many important physiological processes, such as stress responses, appetite control, and motivat...
{"title":"Targeting the relaxin-3/RXFP3 system: a patent review for the last two decades","authors":"Md Toufiqur Rahman, Hetti Handi Chaminda Lakmal, Javeena Hussain, Chunyang Jin","doi":"10.1080/13543776.2024.2338099","DOIUrl":"https://doi.org/10.1080/13543776.2024.2338099","url":null,"abstract":"The neuropeptide relaxin-3/RXFP3 system belongs to the relaxin/insulin superfamily and is involved in many important physiological processes, such as stress responses, appetite control, and motivat...","PeriodicalId":12314,"journal":{"name":"Expert Opinion on Therapeutic Patents","volume":"59 1","pages":""},"PeriodicalIF":6.6,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140571073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}