Fusion proteins are generating a lot of excitement these days because of their targeted use in therapeutic treatments of cancer, autoimmune diseases, and metabolic diseases. The webcast “Recent Trends In The Development and Manufacturing of Fusion Proteins As Therapeutics” examines the practical applications of fusion proteins and the challenges that manufacturers face.

Created by joining two or more genes originally coded for separate proteins or protein domains, a fusion protein results in a single polypeptide that includes functional properties from both genes. These functional properties can include:

• Biological activity

• Receptor or tumor targeting and binding

• Increased serum half life

• Immune system activation or modulation.

Two types of fusion proteins are used today. Fc fusion proteins, which offer increased biological half-life and greater therapeutic exposure, are the most popular. Non-Fc fusion proteins, which are designed to deliver specific combined functions, are quickly becoming accepted as scientists increase their understanding of how diseases progress.

The use of fusion proteins is enabling the pharmaceutical industry to simplify production, product release, and delivery of beneficial therapeutics. Plus, because fusion proteins are nonnative functional combinations, they can be patented — extending the lifecycle for off-patent products and providing a smart marketing opportunity for nonproprietary protein products.

Additionally, fusion proteins offer pharmaceutical companies opportunities to market their therapeutic advantages: With fusion proteins, patients typically experience fewer side effects, require less frequent dosing, and notice greater biological activity. This means consumers can see greater benefits from medicines and treatments developed using fusion proteins — and often in less time.

However, in the production of fusion proteins for clinical trials, manufacturers face some challenges: production of the protein and purification of the fusion molecules.

From a production viewpoint, fusion partners might have different properties that are difficult to manufacture together. A protein domain, for instance, might fold improperly or aggregate and cause purification difficulties. Formulas, too, can be difficult to stabilize because of the differing stability properties of each gene in the fusion.

Because fusion proteins are created by molecular biologists instead of nature, stability and expression rates can be uncertain heading into clinical trials. Also, each domain retains at least some of the properties of the parent molecule (e.g., pH sensitivity) that the other domain might not have. Purity, then, is difficult to predict and manage in any given fusion protein clinical trial.

Despite the challenges, eight companies are currently marketing fusion protein products. Amgen, for example, produces Enbrel, a TNF blocker, and Nplate, a bone marrow stimulator. More companies are expected to produce fusion protein therapeutic treatments in the coming years. Laureate Pharma, for example, is currently the contract manufacturer for Enobia Pharma, which is in a phase 1 clinical study in the United States for a recombinant fusion protein targeting Hypophosphatasia.