How Specific Antibody Drugs Are Stabilized for Storage and Use

Genentech's 2013 patent details a precise recipe for an antibody drug, like Pertuzumab, using a special buffer, sugar, and cleaning agent to keep it stable for patients.

What it covers

This patent describes a very specific liquid recipe, or formulation, for antibody medicines, particularly those targeting a protein called HER2. It claims a combination of an antibody (like Pertuzumab, which targets HER2's domain II), a histidine-acetate buffer to control the acidity (pH between 5.5 and 6.5), a sugar like sucrose to help stabilize it, and a cleaning agent called polysorbate 20. The patent specifies exact amounts, such as antibody concentration between 20-40 mg/mL, sucrose from 60-250 mM, and polysorbate 20 from 0.01-0.1%. This precise mix is designed to keep the antibody drug stable and effective, especially in its liquid form, ready for injection into patients. For example, claim 8 specifies a formulation with about 30 mg/mL Pertuzumab, about 20 mM histidine-acetate, about 120 mM sucrose, and about 0.02% polysorbate 20 at pH 6.0.

What it doesn't cover

• —Antibody formulations not using a histidine-acetate buffer.
• —Formulations with antibodies that do not bind to domain II of HER2.
• —Antibody concentrations outside the 20 mg/mL to 40 mg/mL range.
• —Formulations that have been freeze-dried (lyophilized) before use.
• —Formulations using different sugars or surfactants than specified.
• —Antibody formulations with a pH outside the 5.5 to 6.5 range.

The clever bit

The innovation lies in identifying a precise combination of buffer, sugar, and surfactant at specific concentrations and pH that prevents the antibody from degrading or clumping in a liquid state, making it ready for use without requiring freezing or lyophilization.

Why it matters

This patent is significant because it addresses the critical challenge of keeping complex biological drugs, like monoclonal antibodies, stable and effective outside of a frozen state. Stable liquid formulations are crucial for easier storage, handling, and administration to patients, especially for targeted cancer therapies like Pertuzumab (marketed as Perjeta).

Real-world examples

• 1.Pertuzumab (Perjeta) formulations
• 2.Liquid antibody drug formulations
• 3.Pharmaceuticals requiring high stability