Making High-Concentration Antibody Medicines Stable for Injection

Genentech's 2001 patent on a method to create stable, concentrated antibody medicines that can be easily reconstituted for injection, preventing degradation during freezing and storage.

What it covers

This patent describes how to prepare a stable, concentrated liquid medicine from a frozen-dried (lyophilized) powder containing an antibody. The key is using a special ingredient called a 'lyoprotectant' in a specific ratio (about 100 to 510 moles of lyoprotectant for every 1 mole of antibody). This lyoprotectant protects the antibody from breaking down during the freezing and drying process and while it's stored. When you add liquid back to the powder, you get a medicine with a high concentration of antibody, between 50 to 400 mg/mL, which is stable and ready for injection, often for subcutaneous administration. For example, it covers making a stable, concentrated anti-HER2 antibody formulation ready for use.

What it doesn't cover

• —Formulations where the antibody concentration after reconstitution is less than 50 mg/mL.
• —Formulations that do not use a lyoprotectant during the lyophilization process.
• —Formulations where the molar ratio of lyoprotectant to antibody is outside the range of 100-510:1.
• —Reconstituted formulations that are not isotonic (having the same salt concentration as body fluids).
• —Medicines that are not antibodies, such as small molecule drugs.

The clever bit

The innovation lies in precisely controlling the ratio of lyoprotectant to antibody during lyophilization. This specific ratio ensures the antibody remains stable through the harsh freeze-drying process and storage, allowing for a much higher concentration upon reconstitution than previously thought possible without damaging the antibody.

Why it matters

This patent is significant because it enabled the development of highly concentrated antibody-based therapies. Many complex biologic drugs, like monoclonal antibodies, are fragile. This invention provided a way to stabilize them in a dried form and then reconstitute them at high concentrations suitable for convenient patient self-administration, like subcutaneous injections, rather than requiring intravenous infusions.

Real-world examples

• 1.Genentech's Herceptin (trastuzumab) formulations
• 2.Other lyophilized monoclonal antibody therapies
• 3.Biologic drug products requiring high concentration and stability