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.
