A snapshot of noteworthy recent developments in the patent literature of relevance to pharmaceutical and medical research and development.
Claudin-18.2 is an overexpressed molecule in gastric cancer, which is why it is considered a potential therapeutic target. WO2024082060 describes trispecific antibodies directed against CDLN-18.2/CD3/CD28, and gastric cancer treatment method. These antibodies exhibit cytotoxic activity, in coculture with primary human CD3+ T lymphocytes, against gastric cancer cells expressing CLDN-18.2, as well as an inhibition of tumor growth rate in a murine model of gastric cancer. The trispecific structure, in particular the CD3 and CD28 binding domains, induce optimal co-stimulation of effector T cells, suggesting that these antibodies are potential candidates for clinical trials for the treatment of gastric cancer associated with high levels of CDLN-18.2 expression.
INTRODUCTION:Mesothelin protein is an overexpressed molecule in epithelioid mesothelioma, epithelial ovarian cancer, and pancreatic adenocarcinoma, which is why it is considered a potential therapeutic target. AREAS COVERED:WO2024082060 patent describes a trivalent bispecific antibody directed against MSLN/CD3/MSLN, and lung cancer treatment method. This antibody exhibits binding activity to MSLN-containing tumor cells, as well as inhibition of tumor growth rate in murine models of lung and ovarian cancer. EXPERT OPINION:The trispecific structure suggesting that this antibody is a potential candidate for clinical trials for the treatment of lung cancer associated with high levels of MSLN expression.
INTRODUCTION:Since CD38 is a protein expressed at high levels in multiple myeloma cells, it is an ideal target for antibody design for treatment. AREAS COVERED:Patent US11905332, which describes two anti-CD38/CD28 bispecific antibodies (bsAb6031 and bsAb7945) with the potential for the treatment of multiple myeloma, was evaluated. The results described in the patent show that the anti-CD38/CD28 bispecific antibodies caused elevated in vitro cytotoxicity in tumor cells through increased proliferation of CD4+ and CD8+ cells, and the release of IFN-γ, IL-2, and TNF-α, as well as efficacy in a mouse model of multiple myeloma. EXPERT OPINION:Anti-CD38/CD28 bispecific antibodies have the potential to be used alone or in combination with other antibodies, including anti-BCMA/CD3 antibodies, for the treatment of multiple myeloma.
INTRODUCTION:Proteolysis Targeting Chimeras (PROTACs) represents a groundbreaking advancement in drug discovery and targeted protein degradation. Unlike traditional small-molecule inhibitors, PROTACs leverage the cell's natural protein degradation machinery to selectively degrade pathogenic proteins, offering significant therapeutic potential for previously undruggable targets and complex diseases such as cancer and neurodegenerative disorders. Understanding the regulatory landscape governing their approval is crucial as their development accelerates. AREAS COVERED:This review provides an overview of recent patents, regulatory considerations, emerging concerns, and future perspectives of PROTACs in cancer management. EXPERT OPINION:From a regulatory perspective, PROTACs present unique challenges and opportunities. Their dual-functional nature requires a nuanced approach to classification and approval, blending small-molecule and biologic regulatory frameworks. Specific guidelines addressing pharmacokinetic and pharmacodynamic profiles are needed. Comprehensive preclinical evaluation and robust clinical trial designs are essential to manage off-target effects and immunogenic responses. The collaboration between regulatory bodies, academia, and industry is crucial for establishing a clear pathway for PROTAC approval. Future considerations must account for advancements in PROTAC technology to ensure safe and effective therapies reach patients. While PROTACs hold immense promise, their regulatory journey requires tailored guidelines and rigorous evaluation to realize their full potential.
The oxadiazole derivatives are part of the azole family and have drawn significant interest in medicinal chemistry due to their wide range of biological activities and promising pharmacological profiles. This patent spotlight highlights the developments of the oxadiazole-based compounds reported between 2020 and 2024, with applications in treating diseases such as cancer, bacterial infections, metabolic disorders, and neurodegenerative conditions. These compounds act through various mechanisms, including enzyme inhibition, receptor modulation, and disruption of microbial and cancer cell pathways. Their structural flexibility allows for the design of novel molecules targeting specific therapeutic areas. The spotlight on these recent patents underscores oxadiazole derivatives' growing importance in drug discovery, offering potential advancements in efficacy and safety for future therapeutic agents.
Theranostics represents the state-of-the-art in precision oncology treatment, and is gaining momentum because of the potential to help improve outcomes for even late-stage cancer patients. Pairs of identical (or very similar) molecules are labeled with both diagnostic and therapeutic radionuclides, and used to both image and treat cancer. The FDA approval and commercialization of theranostics for neuroendocrine tumors and prostate cancer has spurred development of new theranostics as well as significant venture and pharma investment, such that both academic medical centers and companies are working to advance the field. One theranostic target of interest is the Fibroblast Activation Protein (FAP) because its expression in many different tumor types offers potential for a pan-cancer theranostic. In this Patent Spotlight, we present the first analysis of patents issued for FAP-targeting radiopharmaceuticals, providing perspective on current trends and challenges as well as future directions.
A snapshot of noteworthy recent developments in the patent literature of relevance to pharmaceutical and medical research and development.
Poly (lactic-co-glycolic acid) (PLGA) is a highly efficient biodegradable polymeric nanoparticle (NP). Owing to its low toxicity, controlled and sustained release qualities, and biocompatibility with tissue and cells, the US FDA has approved its usage in drug delivery systems. The manufacturing and characterization techniques, surface changes, encapsulation of anticancer medicines, active or passive tumor targeting, and various PLGA nanoparticle release methods have been explored in the research arena in the past decade and patents have been filed across the globe. This review covers nanotechnology-backed PLGA patent literature for various types of cancers available on distinguished and eminent patent databases like 'Espacenet' and 'Patent Scope' ranging within a time frame from 2008 to 2024. This review is the first ever reported compilation of the state-of-the-art patent-based literature in PLGA nanoparticles. This review will pave a path for researchers of the present era and future, to understand the research landscape in PLGA nanoparticles and cancer therapy and pave a path for further connective research in the arena of PLGA-based nanoparticles and cancer formulation development.
PI3K and AKT signaling pathway has been linked to the pathophysiology of various diseases. This pathway has emerged as a crucial therapeutic strategy for cancer and other diseases. To better understand recent development of PI3K and AKT, a patent-based landscape study was performed. The results shows that both PI3K and AKT targets have shown prolific patent filings over the past 20 years. This study is the first to depict the therapeutic applications of both PI3K and AKT targets based on a patent big data analysis. Ten key therapeutic applications were identified, with over 77% of patents related to anti-cancer therapy for both PI3K and AKT targets. Additionally, our findings show that combination therapy is a distinguishing feature for drugs targeting both PI3K and AKT. The average time from patent application to drug approval for PI3K target drugs is 8.8 years. PI3K target drugs obtain market approval faster compared to AKT drugs. Approximately, 2 years of patent term extension could be obtained if the time from the patent application date to the drug approval date is less than 10 years.
Obviousness-type double patenting is allowed only in the US, but only if a terminal disclaimer and the same ownership are made for the expiry of the patent. Historically, this provision has hampered the entry of generic and biosimilar drugs due to the legal complexity and cost burden of resolving patent thickets accumulated by the originator companies. The United States Patent and Trademark Office (USPTO) proposed a change in the ruling in March 2024 to avoid double patenting if the patent to which it is tied in terminal disclaimer has any claims that have been invalidated as anticipated or obvious. This rule change aimed to promote innovation and competition by deterring strategies that leverage multiple patents for obvious variants to obstruct competitors. However, after receiving 349 comments on the proposed rule change, the USPTO withdrew its plan in December 2024 despite most comments favoring it. In a contrary move, the USPTO secured a court ruling that the terminal disclaimers do not apply to extended patent expiry due to the failure of the USPTO to prosecute a patent on a timely basis. The double patenting must end to enable more affordable generic and biosimilar drugs.
Primary Amoebic Meningoencephalitis (PAM) is a severe and often fatal infection caused by the free-living amoebae Naegleria fowleri. This condition typically results from exposure to contaminated warm freshwater/inadequately treated recreational water/or ablution/nasal irrigation with contaminated water. The management of PAM is hindered by the absence of effective treatment coupled with challenges in early diagnosis. This review explores emerging patents that could be utilized for the treatment, diagnosis of PAM, as well as water treatment. Recent patents from the past five years, along with research and innovations are reviewed and categorized into therapeutic agents, water treatment technologies, and diagnostic methods. It is hoped that collaboration and awareness between pharmaceutical companies, water industries, and academic institutions is essential for advancing effective strategies against this severe central nervous system pathogen.
A snapshot of noteworthy recent developments in the patent literature of relevance to pharmaceutical and medical research and development.
The release of active agents in tumors rather than normal tissues, limits systemic exposure and toxicities. Targeting over-expressed esterase enzyme in the tumor microenvironment can selectively release immune-active agents like Programmed Death-1 (PD-1) and PD-1 ligand inhibitors from ester-sensitive lipid nanocarriers, offering a novel approach compared with conventional therapies. PD-1 and PD-L1 association cause T-cell inactivation, whereas blocking their association improves their cytotoxic mechanism. The patent application US2022/0080051-A1 discloses a novel immune-active agent conjugated with lipid to form a nanocarrier for esterase-sensitive release. These nanocarriers selectively enter leaky vasculature of tumors through enhanced permeability and retention effect, undergo ester cleavage to release agents, and are reported to increase bioavailability by 24 times. Further, with other agents or alone it achieves targeted synergistic cancer therapy. Also, the current patent spotlight delves into the crucial formulation considerations necessary for obtaining successful approval of lipidic nano products from relevant regulatory authorities.
Type-2 diabetes mellitus (T2DM) is a complicated long-term disorder associated with metabolism that is identified by insulin resistance, imbalance in glucose regulation and reduced secretion of insulin. GLP-1(Glucagon-like peptide-1) is an incretin mimetic that has excellent effects on the regulation of blood glucose levels and also the management of disorders associated with vital organs. GLP-1 agonist is an effective class of drug for the treatment of type-2 diabetes mellitus and associated complications. Liraglutide is one of the potent drugs of this class having similar effects as biological GLP-1. This review includes clinical trials and patents related to the pharmaceutical formulation, synthesis and biological action of liraglutide.
The glucokinase enzyme (belongs to the hexokinase family) is present in liver cells and β-cells of the pancreas. Glucokinase acts as a catalyst in the conversion of glucose-6-phosphate from glucose which is rate-limiting step in glucose metabolism. Glucokinase becomes malfunctional or remains inactivated in diabetes. Glucokinase activators are compounds that bind at the allosteric site of the glucokinase enzyme and activate it. This article highlights the patent and recent research papers history with possible SAR from year 2014-2023. The data comprises the discussion of novel chemotypes (GKAs) that are being targeted for drug development and entered into clinical trials. GK activators have attracted massive interest since successful results have been reported from clinical trials data.
Three-dimensional (3D) printing is one of the most flexible technologies for preparing tablets, offering controlled drug release profiles. The current patent describes the preparation of immediate-release 3D-printed tablets of hydrochlorothiazide to improve disintegration and dissolution profile. The patent involves the preparation of drug-loaded filament via hot-melt extrusion and utilizing the same filaments for printing 3D-printed tablets using fused deposition modeling. The tablets were printed with different shapes and sizes by incorporating channels within the tablet spaces, termed as gaplets. The introduction of channels within the tablet design improves the disintegration and dissolution profile of the drug significantly. The morphological characteristic of 3D-printed tablets was studied by using scanning electron microscopy and revealed the presence of gaplets in the tablets.
A snapshot of noteworthy recent developments in the patent literature of relevance to pharmaceutical and medical research and development.
