Expert Opinion on Therapeutic Patents最新文献

Introduction: The glucagon receptor (GCGR) plays a pivotal role in diabetes management. While small molecule GCGR antagonists (GCGRAs) offer several advantages, including glycemic control, oral bioavailability, and cost-effectiveness, their clinical development is hampered by safety concerns. Recent structural and mechanistic insights have elucidated ligand binding and biased signaling and informed the rational design of GCGRAs.

Areas covered: This review presents an overview of small molecule GCGRAs between 2020 and 2024, drawing information from existing patents, peer-reviewed literature, and clinical data retrieved from the PubMed, Web of Science, SciFinder, and Derwent Innovation databases.

Expert opinion: In this observation period, innovation ownership shifted from pharmaceutical companies to academic institutions, which are emerging as key applicants for novel chemotypes. Such a significant shift reflects a broader divergence in innovation strategies, with academia increasingly exploring new chemotypes supported by deep learning and virtual screening, while companies focus on maintaining and optimizing established scaffolds. Furthermore, advances in structural and mechanistic studies have clarified ligand binding and biased signaling, informing the rational design of high-specificity, high-affinity GCGRAs. However, clinical investigations are warranted to assess whether these compounds can overcome current developmental bottlenecks, restore glucose homeostasis, and address safety concerns.

Introduction: Mixed-spectrum kinase structural domain-like protein (MLKL), which emerged as a pivotal regulator in biomedical research, plays a critical role in necroptotic pathways. Recent advancements have underscored the therapeutic potential of MLKL modulators.

Areas covered: This review focuses on the patent literature covering MLKL-targeted molecules published from 2023 to July 2025. Patent and literature searching were performed using SciFinder, Espacenet, and PubMed databases.

Expert opinion: Research on MLKL modulators has seen significant progress in recent years, with many preclinical studies documenting various modulators, but the development of MLKL modulators, particularly activators, remains in its early stages due to challenges in specificity, efficacy, and bioavailability. Advancing therapeutic strategies will require a deeper understanding of MLKL-driven pathologies, optimizing existing modulators, and discovering new ones. The notable increase in natural product-derived MLKL inhibitors highlights the potential of identifying and modifying natural products as an effective approach for developing novel inhibitors.

Introduction: Toll-like receptors (TLRs) play a key role in cancer immunotherapy by harnessing the immune system's natural response to target and fight tumors. Among the various TLRs, mainly TLR3, TLR4, TLR7, TLR8, and TLR9, have been investigated for their ability to modulate immune responses, improve tumor recognition, and enhance the efficacy of conventional treatments like chemotherapy and radiotherapy.

Areas covered: This review provides an in-depth analysis of patents filed from 2014 to 2024 that explored TLR-targeting strategies in cancer therapy. TLRs trigger the release of pro-inflammatory cytokines such as IFN-γ, TNF-α, IL-12, and IL-6, which promote anti-tumor immunity by enhancing T-cell activation and dendritic cell maturation. TLR-based therapies have shown promise by stimulating innate and adaptive immunity, leading to increased tumor cell death.

Expert opinion: TLR agonists have been shown to, reduce treatment-related side effects, and inhibit tumor growth. However, challenges such as immune-related adverse events, including cytokine storms, and limited efficacy in specific tumor types persist. Advances in delivery systems, such as nanoparticles, liposomes, and conjugates, further enhance the targeting and effectiveness of TLR-based therapies while minimizing toxicity. The ongoing exploration of TLR agonists and their integration into combination therapies holds significant promise for improving cancer immunotherapy and patient outcomes.

Introduction: Topoisomerase (topo) II inhibitors continue to represent a promising approach in anticancer therapy, although their clinical application is hampered by drug resistance and dose limiting toxicities.

Area covered: We performed a critical analysis of patent literature from January 2016 to January 2025 on topo II inhibitors in oncology using the online databases Espacenet, Wipo, and Google patent.

Expert opinion: Substantial progress in the development of novel topo II inhibitors through synthetic chemistry, natural product isolation, molecular modification, and in silico screening was recorded. These compounds belong to different chemical classes and mainly exhibit in vitro cytotoxicity in a low micromolar range, comparable to or greater than that induced by clinically established topo II inhibitors such as doxorubicin and etoposide. Some patented compounds showed catalytic inhibition of topo II enzyme, offering a safer and more effective alternative to topo II poisons. Despite encouraging in vitro data, only a few patents provide in vivo data or mechanistic insights, and none have progressed to clinical trials, highlighting a gap between preclinical innovation and clinical translation. Future research needs advancing in clinical development to fully realize the therapeutic potential of next-generation topo II inhibitors.

Introduction: Bruton's tyrosine kinase (BTK) is a critical regulator in the pathogenesis of B-cell malignancies, inflammatory diseases, and autoimmune diseases. In recent years, BTK inhibitors have been a hot topic in drug development, with promising therapeutic prospects. Six BTK inhibitors have been approved, and several (including PROTAC) are undergoing clinical research.

Areas covered: This review provides a comprehensive analysis of BTK inhibitor mechanisms and synthesizes recent advancements documented in patent literature (2019-2024), with particular emphasis on structural innovations and therapeutic applications. Web of Science, PubMed, SciFinder, WIPO, EPO, USPTO and CNIPA databases were used for searching the literature and patents for BTK inhibitors.

Expert opinion: In recent years, many new drug development strategies proposed by medicinal chemists, such as multi-target inhibition, deuterium substitution, macrocyclization, and targeted protein degradation strategy (such as PROTAC), may provide guidance for the development of novel BTK inhibitors and overcome the problems of existing BTK inhibitors. Despite many challenges, BTK inhibitors have great potential in treating cancer and other diseases. With the application of new drug development strategies, the development of the next generation of BTK inhibitors may be promising.

Background: Helicase-primase is an interesting target for small-molecule therapy of herpes simplex virus (HSV) infections. With amenamevir already approved for varicella-zoster virus and herpes simplex in Japan and with pritelivir's granted breakthrough therapy designation for the treatment of acyclovir-resistant HSV infections in immunocompromised patients, the target has sparked interest in helicase-primase inhibitors.

Areas covered: Here, we analyze the series of patent applications from Assembly Biosciences (published between 03/2024 and 03/2025) covering their drug candidate ABI-5366 together with additional data from poster presentations, press releases and company updates. This me-too approach on the old Bayer urea series is currently in clinical phase I (NCT06385327) and the modification is the bridging of the two urea nitrogens via an alkylene linkage.

Expert opinion: The chemical structure for 1,3-disubstituted tetrahydropyrimidin-2(1H)-one derivative ABI-5366 is presented and its potential opportunities and limitations as a long-acting oral administration or injectable depot drug compared to other HPIs are discussed.

Introduction: Traf2- and Nck-interacting kinase (TNIK) is a crucial player in various intracellular signaling pathways, including Wnt/β-catenin, cytoskeleton organization, and immune activation. It phosphorylates several key target genes and is widely expressed in different organ systems, such as neural, gastrointestinal, lung, liver, and kidney tissues. TNIK has been implicated in multiple different disease areas, including oncology, neurological diseases, and fibrosis.

Area covered: This review provides an update of small molecule TNIK inhibitors in patents published from 2008 to 2024.

Expert opinion: Despite over 10 patents disclosing multiple scaffolds since 2008, only one inhibitor, INS018_055, has advanced to clinical trials to treat idiopathic pulmonary fibrosis. For the oncology indications, this is largely due to complexities in the relationship between TNIK and oncogenic pathways. Additionally, key characteristics of the molecules, such as kinase selectivity, physicochemical properties, and pharmacokinetic profiles, have played significant roles in determining whether the molecules are drug-like enough to advance to clinical trials.

Introduction: The drug patent linkage system plays a crucial role in achieving a balance between protecting drug innovation and ensuring the accessibility of generic drugs. Currently, this system has been implemented in many countries. This review aims to provide policy guidance and a reference basis for relevant stakeholders, while also offering valuable insights to other countries considering the implementation of the patent linkage system globally.

Areas covered: This review provides a comprehensive summary and comparative analysis of the patent linkage systems in the United States, Canada, South Korea, Singapore, and China, with a focus on China's recently implemented system and its outcomes. The data presented are derived from the official websites of the China NIPA, the IPC, and the NMPA's Drug Patent Information Registration Platform.

Expert opinion: This main goal of this system is to balance the interests of both parties through an efficient dispute resolution mechanism, while policy formulation is only the initial stage of the reform process and requires continuous improvement throughout the implementation phase. The author employed descriptive statistical methods to systematically analyze relevant data, providing valuable insights to colleagues in the field both domestically and internationally.

Introduction: Antimicrobial resistance (AMR) and the emergence of multidrug-resistant bacteria, including Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. (ESKAPE) pathogens, have significantly reduced the effectiveness of antibiotics. In this context, bacteriophage therapy offers a promising alternative, targeting specific bacterial strains, disrupting biofilms, minimizing side effects, and preserve beneficial microbiota.

Areas recovered: This review focuses on patent applications and patents granted up to 18 October 2024, related to the application of bacteriophages or their derivatives in treating infections caused by ESKAPE pathogens, as well as the methods for selecting bacteriophages.

Expert opinion: Phage-based strategies to overcome AMR have piqued the interest of the scientific community owing to the limited efficacy of new antimicrobial agents. Bacteriophages, co-evolved with antimicrobial-resistant bacteria, offer a diverse and cost-effective arsenal, especially beneficial for low- to middle-income countries. This review examines various patents on phage applications, including those on computational methods used for improving phage cocktail design, classical phages or phage-derived proteins, and potential combinations of antimicrobial agents and phages. The increasing number of phage-related patents, especially in China and the United States, suggests that the antimicrobial activity of bacteriophages is a research hotspot.

Introduction: Tumor cell heterogeneity poses a challenge to monotherapy, as a single drug cannot kill all heterogeneous cancer cells of a tumor. The surviving cells may develop resistance, potentially leading to tumor recurrence. The combination therapy targets the disease through multiple mechanisms. Combinations of histone deacetylase (HDAC) inhibitor(s) with other inhibitor(s) have represented promising cancer chemotherapeutics by altering the epigenetic landscape of cancer cells by restoring acetylation and reactivating tumor suppressor genes, leading to cell cycle arrest, promoting apoptosis, and thus inhibiting cancer cell proliferation.

Areas covered: The patent literature (2020-present) on rational combinations of HDAC inhibitor(s) for cancer chemotherapy has been searched and reviewed from Google Patents, Patentscope, Espacenet, WIPO, and USPTO to provide an expert opinion on rational combinations for improved, optimized, and precise cancer therapy. This first part of a two-part review highlights the patent granted for the combination.

Expert opinion: The combination of HDAC inhibitors with other inhibitors, including Janus kinase (JAK), aurora kinase, tubulin, Sirtuin 2, and/or topoisomerase inhibitors, demonstrated a synergistic anti-cancer effect. Dual and multi-target inhibitors showed enhanced therapeutic efficacy in relapsed and refractory cases characterized by epigenetic dysregulation via histone modifications and alterations that contribute to disease progression.