A Systematic Method for the Improvement of Protein and Antibody Stability

Introduction

Proteins and antibodies are used for a wide variety of applications such as therapeutics, diagnostics, imaging, bioremediation, sensor, and research tools. The U.S. Food and Drug Agency has approved 23 antibodies, of which eight have reached blockbuster status ($1 billion or more in annual sales revenue). Nearly 200 antibodies are at various stages in development. The global market for antibody therapeutic was $25 billion in 2007, and is expected to reach $45 billion by 2012. It is one of the fastest growing sectors in the pharmaceutical industry. Average annual growth rate for antibody therapeutic market is 11.5%.

Problem

A majority of commercially available antibodies are unstable. Consequently, they have a lower serum half-life than naturally occurring antibodies and require refrigeration for long-term preservation. This requirement limits the application of antibodies to controlled environments. Methods currently used to increase the stability of antibodies are costly, time-consuming, and highly unpredictable.

Solution

Argonne has developed a proprietary antibody engineering strategy to improve antibody stability. The strategy consists of replacing carefully selected amino acid residues in variable domain using site-directed mutagenesis, and testing the mutants for stability and function. The method is systematic, fast, inexpensive, and highly predictable. The method is also applicable to proteins.

Advantages and Applications

Proteins and antibodies stabilized using this method offer advantages such as lower cost of production, simplified formulation, longer shelf life, decreased dosage, reduced side effects, lower price, and ability to deploy in field applications. The method can be used to fine-tune the stability of antibodies to generate multiple products from the same antibody for different applications. For instance, antibodies with low stability are well-suited for imaging and radiotherapy applications. On the other hand, antibodies with medium stability are preferred for therapeutic applications, and antibodies with high stability are desirable for diagnostic and biosensor applications. Stabilized antibodies generated by using the method can be used in applications such as therapeutics, diagnostics, bioremediation, and robust biosensors to detect infectious agents, toxins, and explosives for field use.

Technology Status

The method has been used to increase the stability of antibodies against biodefense targets such as anthrax spores and botulinum neurotoxin. Further research is under way to develop a comprehensive biosensor to detect all serotypes of botulinum neurotoxin.

IP Position

A patent application on this technology has been filed.

Notification

Argonne seeks to receive expression of interest from qualified parties within the opportunity period. Qualified parties are those organizations that can demonstrate the technical expertise, capability, strategy, and resources to maximize the commercial opportunity of the subject technology