Expert Opinion on Therapeutic Patents最新文献

{"title":"Small molecule and peptide CXCR4 antagonists. A patent review from 2019 to 2024.","authors":"Zafer Sahin, Yesim A Tahirovic, Jiafeng Geng, Lawrence J Wilson, Dennis C Liotta","doi":"10.1080/13543776.2025.2462848","DOIUrl":"10.1080/13543776.2025.2462848","url":null,"abstract":"<p><strong>Introduction: </strong>The chemokine receptor CXCR4 has been under intense study due to the central role it plays in immune system regulation and the pathology of human disease. Although the first CXCR4 drug plerixafor emerged over a decade ago (2007), recently the first peptide (motixafortide, 2023) and the first oral small molecule (mavorixafor, 2024) CXCR4 antagonists became FDA approved.</p><p><strong>Areas covered: </strong>This article describes patent documents published during the period of 2019 through 2024 for both small molecule and peptides. This IP includes few new chemotypes, with most being extensions of existing structural classes. There is also less significant IP covering peptide-based therapeutics than those covering small molecules. Notably, multiple therapeutic uses have also emerged. Patents were searched from SciFinder (CAS) and Google Patents with the term <i>CXCR4 antagonists</i>. Patents were selected according to whether they fit into the classification of small molecules or peptides.</p><p><strong>Expert opinion: </strong>In the last 5 years there has been significant advancement in CXCR4 antagonists as gauged by the FDA approval of two drugs. The search for second and third generation compounds will be the focus of future efforts with new uses and better properties which likely could come from some of the IP described herein.</p>","PeriodicalId":12314,"journal":{"name":"Expert Opinion on Therapeutic Patents","volume":" ","pages":"357-369"},"PeriodicalIF":5.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381980","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}

{"title":"A patent review of peptidylarginine deiminase 4 (PAD4) inhibitors (2014-present).","authors":"Sheenagh Grace Aiken, Thomas Grimes, Shonagh Munro, Tryfon Zarganes-Tzitzikas, Nicholas Barrie La Thangue, Paul Edward Brennan","doi":"10.1080/13543776.2025.2484366","DOIUrl":"10.1080/13543776.2025.2484366","url":null,"abstract":"<p><strong>Introduction: </strong>PAD4 mediates the post-translational modification of arginine residues into citrulline which can have profound effects on protein structure, function and interactions. Protein citrullination and neutrophil extracellular trap (NET) formation associated with increased PAD4 activity have been implicated in the development of autoimmune conditions, cardiovascular diseases, neurodegenerative disorders, and cancer. PAD4 inhibitors have been shown to suppress citrullination and NETs formation.</p><p><strong>Areas covered: </strong>This review covers 10 years of industrial drug discovery campaigns reported in 28 patent applications from 10 companies. Cortellis, the World Intellectual Property Organization website, Scopus and SciFinder were used to search the patent literature using the keywords 'PAD4' and 'PAD4 inhibitor.' Most of the reported inhibitors share the same core scaffold with varied decoration of different complexity, including highly functionalized macrocycles, with some in vivo and pharmacokinetic (PK) data reported for selected examples.</p><p><strong>Expert opinion: </strong>Despite PAD4's clear involvement in multiple disease pathways, its detailed mechanism remains insufficiently understood. Selective and potent compounds with improved PK properties have been provided but most research on PAD4 is still at the experimental stage or preclinical development; the most promising is JBI-1044, at the IND stage, while some companies have turned to antibodies despite considerable previous investment in small molecules.</p>","PeriodicalId":12314,"journal":{"name":"Expert Opinion on Therapeutic Patents","volume":" ","pages":"1-11"},"PeriodicalIF":5.4,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709185","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}

{"title":"An updated patent review of antitumor macrocyclic kinase inhibitors (2019 present).","authors":"Xintao He, Lu Chen, Shuangshuang Wu, Zhichao Chen, Wufu Zhu, Dan Qiao","doi":"10.1080/13543776.2025.2484368","DOIUrl":"10.1080/13543776.2025.2484368","url":null,"abstract":"<p><strong>Introduction: </strong>Small molecule kinase inhibitors are crucial in the treatment of tumors, and the development of novel inhibitors is a primary approach to combat the continuous emergence of drug resistance. Macrocyclization has emerged as a cutting-edge strategy to enhance the potency, selectivity, and pharmacokinetic properties of these inhibitors by altering their biological and physicochemical characteristics compared to their acyclic counterparts.</p><p><strong>Areas covered: </strong>The present article provides a comprehensive overview of the recent advancements in macrocyclic small molecule inhibitors and their inhibitory activities against various cancer cells, which have been patented since 2019.</p><p><strong>Expert opinion: </strong>To date, small-molecule kinase inhibitors have demonstrated remarkable therapeutic efficacy in clinical settings. Recent patents have primarily focused on addressing challenges associated with resistance mutations. Despite the significant success achieved in developing selective kinase agents, the identification of new targets and emergence of novel mutations necessitate the development of novel small-molecule inhibitors. Macrocyclic compounds possess distinctive conformational constraints, enhanced inhibitor potency and selectivity, as well as favorable pharmacokinetic properties, rendering them safe, efficient, selective, low-toxicity agents with unique structural characteristic.</p>","PeriodicalId":12314,"journal":{"name":"Expert Opinion on Therapeutic Patents","volume":" ","pages":"1-15"},"PeriodicalIF":5.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700032","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}

{"title":"RORγt inhibitors in clinical development for the treatment of autoimmune diseases: challenges and opportunities.","authors":"Nannan Sun, Yonghui Wang","doi":"10.1080/13543776.2025.2482936","DOIUrl":"10.1080/13543776.2025.2482936","url":null,"abstract":"<p><strong>Introduction: </strong>Nuclear receptor retinoid-related orphan receptor gamma-t (RORγt) is a major transcription factor for Th17 cell differentiation and IL-17 production. RORγt has been considered as a promising drug target for the treatment of IL-17-mediated inflammatory diseases. Numerous small molecule inhibitors have been discovered, and more than 20 of RORγt inhibitors have been advanced to clinical trials. However, none of these compounds has yet achieved market approval.</p><p><strong>Areas covered: </strong>This manuscript summarizes the development of 22 clinical-stage RORγt inhibitors, including their structures, patent applications, and clinical trial status, based on publications and patents available up to November 2024.</p><p><strong>Expert opinion: </strong>The discovery of RORγt inhibitors was considered as an exciting field for the development of small molecular treatments, which has gone through a boom period in the past 10 years. However, some of the leading RORγt inhibitors recently failed in clinical trials due to lack of efficacy or having some safety concerns, although a few small molecule candidates targeting RORγt are still in trials and more in preclinical studies. Realizing the challenge, researchers started to develop different approaches such as dual targeting or exploring new indications, utilizing the potential value of RORγt inhibitors.</p>","PeriodicalId":12314,"journal":{"name":"Expert Opinion on Therapeutic Patents","volume":" ","pages":"1-13"},"PeriodicalIF":5.4,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662738","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}

{"title":"An updated patent review of EZH2 inhibitors (2024-present).","authors":"Guoquan Wan, Siyan Li, Qifan Tang, Huapei Qiu, Qiangsheng Zhang, Luoting Yu","doi":"10.1080/13543776.2025.2483399","DOIUrl":"10.1080/13543776.2025.2483399","url":null,"abstract":"<p><strong>Introduction: </strong>EZH2 forms the PRC2 complex with SUZ12 and EED. As a crucial catalytic subunit of PRC2, EZH2 modifies histone H3K27 via its SET domain, resulting in chromatin condensation and suppressing the transcription of related target genes. EZH2 not only functions in PRC2-dependent transcriptional repression but can also activate gene expression in PRC2-independent circumstances or regulate the activity of downstream genes via its own activating mutations. On the basis of the critical role of EZH2 in cancer, the development of inhibitors targeting EZH2 provides a new strategy for cancer therapy.</p><p><strong>Areas covered: </strong>The purpose of this review is to summarize the molecular mechanisms of EZH2 inhibitors and emphasize the research progress on EZH2 inhibitors published in the patent literature in recent years. The literature and patent databases of PubMed, Web of Science, SCIFinder, WIPO, USPTO, EPO, and CNIPA were combined to search for more effective EZH2 inhibitors.</p><p><strong>Expert opinion: </strong>Recently, a wide range of structurally diverse EZH2 inhibitors, particularly EZH2 degraders, have been identified. These EZH2 modulators have demonstrated significant potential in treating various diseases, with cancer being a primary focus. The development of small molecules targeting EZH2 with distinct pharmacological effects is poised with numerous opportunities.</p>","PeriodicalId":12314,"journal":{"name":"Expert Opinion on Therapeutic Patents","volume":" ","pages":"1-14"},"PeriodicalIF":5.4,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673687","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}

{"title":"A patenting perspective of fat mass and obesity associated protein (FTO) inhibitors: 2017-present.","authors":"Ze Dong, Yue Huang, Wenyang Xia, Yonggang Liao, Cai-Guang Yang","doi":"10.1080/13543776.2025.2477482","DOIUrl":"10.1080/13543776.2025.2477482","url":null,"abstract":"<p><strong>Introduction: </strong>The fat mass and obesity-associated protein (FTO) catalytically demethylates RNA N⁶-methyl adenosine (m⁶A) modification, dynamically regulates gene expression in eukaryotes. Interestingly, FTO is highly expressed and functions as an oncogenic factor in a wide range of cancers. Therefore, using small-molecule inhibitors to target FTO has been established as a promising therapeutic strategy for combating cancers.</p><p><strong>Areas covered: </strong>Patent literature claiming novel chemical entities as FTO inhibitors disclosed from 2017 to present is available in Espacenet, including dozens of patent documents.</p><p><strong>Expert opinion: </strong>The pivotal influence of FTO demethylase in a particular epigenetic layer of regulation of gene expression renders it promising for FTO to be a therapeutical target for many diseases, including malignant cancers. Several institutions were prompted and have patented chemical frameworks as FTO inhibitors. Remarkedly, the FTO inhibitor CS1 (Bisantrene) has advanced to clinical trials for treating acute myeloid leukemia (AML). The successful advancement of CS1 into clinical trials would continuingly stimulate researches on RNA epigenetic enzymes targeted first-in-class anticancer drug discovery.</p>","PeriodicalId":12314,"journal":{"name":"Expert Opinion on Therapeutic Patents","volume":" ","pages":"1-10"},"PeriodicalIF":5.4,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572510","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}

{"title":"Heterogeneity-Preserving Discriminative Feature Selection for Disease-Specific Subtype Discovery.","authors":"Abdur Rahman M A Basher, Caleb Hallinan, Kwonmoo Lee","doi":"10.1101/2023.05.14.540686","DOIUrl":"10.1101/2023.05.14.540686","url":null,"abstract":"<p><p>The identification of disease-specific subtypes can provide valuable insights into disease progression and potential individualized therapies, important aspects of precision medicine given the complex nature of disease heterogeneity. The advent of high-throughput technologies has enabled the generation and analysis of various molecular data types, such as single-cell RNA-seq, proteomic, and imaging datasets, on a large scale. While these datasets offer opportunities for subtype discovery, they also pose challenges in finding subtype signatures due to their high dimensionality. Feature selection, a key step in the machine learning pipeline, involves selecting signatures that reduce feature size for more efficient downstream computational analysis. Although many existing methods focus on selecting features that differentiate known diseases or cell states, they often struggle to identify features that both preserve heterogeneity and reveal subtypes. To address this, we utilized deep metric learning-based feature embedding to explore the statistical properties of features crucial for preserving heterogeneity. Our analysis indicated that features with a notable difference in interquartile range (IQR) between classes hold important subtype information. Guided by this insight, we developed a statistical method called PHet (Preserving Heterogeneity), which employs iterative subsampling and differential analysis of IQR combined with Fisher's method to identify a small set of features that preserve heterogeneity and enhance subtype clustering quality. Validation on public single-cell RNA-seq and microarray datasets demonstrated PHet's ability to maintain sample heterogeneity while distinguishing known disease/cell states, with a tendency to outperform previous differential expression and outlier-based methods. Furthermore, an analysis of a single-cell RNA-seq dataset from mouse tracheal epithelial cells identified two distinct basal cell subtypes differentiating towards a luminal secretory phenotype using PHet-based features, demonstrating promising results in a real-data application. These results highlight PHet's potential to enhance our understanding of disease mechanisms and cell differentiation, contributing significantly to the field of personalized medicine.</p>","PeriodicalId":12314,"journal":{"name":"Expert Opinion on Therapeutic Patents","volume":"6 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10769187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89169616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A patent review of von Hippel-Lindau (VHL)-recruiting chemical matter: E3 ligase ligands for PROTACs and targeted protein degradation (2019-present).","authors":"Aina Urbina, Alex J Hallatt, Jack Robertson, Alessio Ciulli","doi":"10.1080/13543776.2024.2446232","DOIUrl":"10.1080/13543776.2024.2446232","url":null,"abstract":"<p><strong>Introduction: </strong>The von Hippel-Lindau (VHL) E3 ubiquitin ligase has seen extensive research due to its involvement in the ubiquitin proteasome system and role as a tumor suppressor within the hypoxia signaling pathway. VHL has become an attractive target for proteolysis targeting chimeras (PROTACs), bifunctional molecules that can induce degradation of neo-substrate proteins. The development of VHL inhibitors and PROTACs has seen rapid development since disclosure of the first non-peptidic VHL ligand (2012).</p><p><strong>Areas covered: </strong>Due to the demand for more diverse and sophisticated VHL ligands that can be applied to PROTACs, the number of patents disclosed has risen significantly in the past 5 years. Herein, the wide range of VHL modifications that have been patented since 2019 is covered. Specifically, any new or unique chemical modification to established VHL ligands or PROTACs will be discussed.</p><p><strong>Expert opinion: </strong>The VHL chemical space continues to expand within the patent literature. There are exciting new modifications that can enhance the physiochemical properties of VHL PROTACs and other alterations can improve the affinity of the VHL ligand itself. Further optimization of the VHL chemical space will no doubt lead to the development of more VHL-based therapies and clinical candidates.</p>","PeriodicalId":12314,"journal":{"name":"Expert Opinion on Therapeutic Patents","volume":" ","pages":"1-42"},"PeriodicalIF":5.4,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11875441/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A patent review of small molecular inhibitors targeting EGFR exon 20 insertion (Ex20ins) (2019-present).","authors":"Wenjian Zhu, Junping Pei, Xiaoyun Lu","doi":"10.1080/13543776.2024.2446220","DOIUrl":"10.1080/13543776.2024.2446220","url":null,"abstract":"<p><strong>Introduction: </strong>Mutations in epidermal growth factor receptor (EGFR) kinase domain consistently activate downstream signaling pathways, such as the PI3K/AKT/mTOR and RAS/RAF/MEK, thereby promoting tumor growth. Although the majority of non-small cell lung cancer (NSCLC) patients harboring EGFR mutations are sensitive to existing EGFR tyrosine kinase inhibitors (EGFR-TKIs), there remains an unmet clinical need for effective therapies targeting EGFR Ex20ins mutations, making direct targeting EGFR Ex20ins mutations a promising therapeutic strategy.</p><p><strong>Areas covered: </strong>This review covers the progress of clinical studies targeting EGFR Ex20ins inhibitors and summarizes recent (1 January 2019 - 30 April 2024) patents disclosing EGFR Ex20ins inhibitors available in the Espacenet and CAS SciFinder databases.</p><p><strong>Expert opinion: </strong>An increasing number of EGFR Ex20ins inhibitors are being developed and reported. Existing inhibitors are focused on enhancing the efficacy of EGFR Ex20ins inhibitors and addressing the challenge of targeted resistance by optimizing the second - or third-generation EGFR inhibitors and developing innovative skeleton molecules. Moreover, the development of targeted protein degraders, allosteric inhibitors, and combination therapies provide additional approaches to address EGFR Ex20ins mutations. However, bypass resistance, selectivity, and drug sensitivity still pose challenges in this field.</p>","PeriodicalId":12314,"journal":{"name":"Expert Opinion on Therapeutic Patents","volume":" ","pages":"91-110"},"PeriodicalIF":5.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871905","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}

{"title":"Patent review of novel compounds targeting opioid use disorder (2018-2024).","authors":"Samuel Obeng, Lance R McMahon, Edward Ofori","doi":"10.1080/13543776.2024.2446230","DOIUrl":"10.1080/13543776.2024.2446230","url":null,"abstract":"<p><strong>Introduction: </strong>Opioids have served as a cornerstone in pain management for decades. However, the emergence of increasingly potent synthetic analogs brings forth a range of side effects, including respiratory depression, tolerance, dependence, constipation, and, more importantly, the development of severe and debilitating opioid use disorder (OUD). Search for therapeutics to mitigate OUD has been challenging, and this has called for novel approaches that include the design of small molecules targeting neuronal circuits involved in addiction (opioid, dopamine, serotonin, norepinephrine, and glutamate receptors, etc.).</p><p><strong>Areas covered: </strong>In this review, we retrieve and discuss two dozen (24) relevant patents filed in the past six (6) years that focus on novel small-molecule therapeutics for OUD. The chemical entities disclosed were highlighted, and specific examples were provided where necessary.</p><p><strong>Expert opinion: </strong>Several chemical entities targeting both opioid and non-opioid targets are under consideration for treating OUD. Our search for patents covering such compounds revealed embodiments with diverse chemistry. Understanding the public impact of OUD and the rapidly evolving landscape of substance abuse underscores the urgent need for a thorough reevaluation of strategies to address these challenges. This includes the development of small molecules with unique mechanisms of action for OUD treatment.</p>","PeriodicalId":12314,"journal":{"name":"Expert Opinion on Therapeutic Patents","volume":" ","pages":"165-180"},"PeriodicalIF":5.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002869","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}