US20260007743
2026-01-08
Human necessities
A61K39/39558
The invention addresses the need for a stable, high-concentration formulation of anti-HER2 antibodies, such as Trastuzumab, Pertuzumab, or T-DM1, intended for subcutaneous injection. These formulations incorporate a hyaluronidase enzyme to facilitate administration, alongside stabilizers, a buffering agent like histidine, and a nonionic surfactant. The combination aims to overcome the limitations of intravenous administration by offering a subcutaneous alternative that can be self-administered, reducing the need for hospital visits.
Antibodies are typically administered intravenously, but this method is constrained by solubility and stability issues, as well as the volume of infusion fluid. Subcutaneous injection presents a viable alternative, requiring formulations with high protein concentrations. The invention leverages glycosaminoglycanase enzymes to enhance the interstitial space for injection, addressing challenges like the viscosity and aggregation of proteins that can occur in high-concentration formulations.
Existing antibody products, such as HERCEPTINâ„¢ and AVASTINâ„¢, are formulated for intravenous use, while others like HUMIRAâ„¢ and XOLAIRâ„¢ are designed for subcutaneous administration. However, no highly concentrated anti-HER2 formulations suitable for subcutaneous use are currently available. The invention seeks to fill this gap by providing a formulation that maintains stability and efficacy, even at high concentrations, while minimizing immunogenic reactions caused by protein aggregates.
Formulating high-concentration antibodies is complex due to the potential for increased viscosity and protein aggregation, which can affect manufacturing and administration processes. The invention involves the use of excipients to reduce viscosity and surfactants to control aggregation. Monitoring and controlling these factors are crucial, as they influence the stability and activity of the therapeutic proteins during storage and use.
The invention specifies formulations containing 50 to 350 mg/ml of anti-HER2 antibody, with a buffering agent in the range of 1 to 100 mM to maintain a pH of 5.5±2.0. This composition is designed to ensure the formulation remains stable over time, preserving the therapeutic efficacy of the antibodies. The inclusion of hyaluronidase aids in increasing the volume that can be safely administered subcutaneously, enhancing patient comfort and treatment efficiency.