Preventing Protein Damage with Extra Methionine

This 1993 patent describes how adding extra methionine to protein-based medicines can prevent them from degrading, especially in liquid or semi-solid forms.

What it covers

This patent details a method to stop proteins, specifically those with a methionine amino acid, from oxidizing and breaking down when stored in liquid or semi-solid medicines. The key is to add extra methionine, an amino acid that is part of the protein, to the preparation. This added methionine acts as a shield, getting oxidized itself instead of the methionine within the therapeutic protein. The patent specifies adding methionine in amounts between 0.01% and 0.3% by weight or volume, ensuring that the therapeutic protein remains stable for storage and use. For example, claim 8 describes using this method with epidermal growth factor in a liquid solution.

What it doesn't cover

• —Methods that do not involve adding methionine to inhibit oxidation.
• —Methods for stabilizing proteins that do not contain any methionine residues.
• —Stabilization of proteins in solid dosage forms (e.g., pills, powders).
• —Adding methionine in concentrations outside the specified range of 0.01% to 0.3%.
• —Inhibiting oxidation of molecules other than polypeptides.

The clever bit

The inventors realized that methionine, an amino acid naturally present in many proteins, is particularly susceptible to oxidation. By adding extra methionine to the formulation, they created a sacrificial agent that preferentially oxidizes, thereby protecting the methionine residues within the therapeutic protein itself.

Why it matters

This patent addresses a critical challenge in biopharmaceutical development: maintaining the stability and efficacy of protein-based drugs. Proteins are delicate molecules prone to degradation, which can render them useless or even harmful. By providing a simple yet effective method to prevent oxidation, this patent likely contributed to the viability of developing and commercializing various protein therapeutics, particularly those intended for topical or injectable use.

Real-world examples

• 1.Ophthalmic solutions containing growth factors
• 2.Creams or ointments with therapeutic proteins
• 3.Liquid formulations of recombinant proteins