Our Technology

Protein-Based Biopharmaceuticals
The development and commercialization of protein-based biopharmaceuticals has revolutionized the practice of medicine. Currently, the biopharmaceutical market is estimated to be well in excess of $40 billion annually. Despite the clinical and commercial successes of a small number of protein-based biopharmaceuticals, it is important to note that the transformation of a biologically active protein into a commercially viable biopharmaceutical is not a trivial process.

First, many proteins are either rapidly degraded, have a short circulating life, or are rapidly excreted when introduced into the bloodstream. Consequently, many protein-based biopharmaceuticals require repeated intravenous infusions for therapeutic efficacy.

Second, repeated injections of a protein-based biopharmaceutical can result in adverse immunological responses and side effects. Finally, the production costs and labor required to manufacture biopharmaceuticals can be substantial.

Protein PEGylation: A Historical Perspective

In the 1970s while at Rutgers University, Abraham Abuchowski and Frank Davis developed a revolutionary delivery system that overcame many of the hurdles impeding the clinical development of therapeutic proteins. They determined that the chemical attachment of polyethylene glycol (PEG) had a multitude of beneficial effects on intravenously administered proteins. Dr. Abuchowski coined the term "PEGylation" to describe the chemical attachment of PEG to proteins and the field of PEGnology was born.

Recognizing the potential scientific and commercial impact of PEGnology, Dr. Abuchowski co-founded Enzon, Inc. with Dr. Davis in 1982 to exploit the technology. During his thirteen year tenure at Enzon, Dr. Abuchowski was the Chairman, CEO, and Chief Scientist. He and his co-workers validated the scientific underpinnings of PEGnology and used it to create, gain FDA approval and commercialize, three protein-based biopharmaceuticals: Adagen (treatment for "Bubble Boy" Disease), Oncaspar (treatment for Acute Lymphoblastic Leukemia in children), and Peg-Intron (a treatment for Hepatitis C), which is currently marketed by Schering-Plough. Recently, several other PEGylated products have been approved, such as Neulasta (Amgen), which is a PEGylated version of Neupogen, Somavert (Pfizer) and PEG-interferon-alpha (Roche). PEGylation has become the biopharmaceutical delivery technology of choice for intravenously administered therapeutic proteins.

What is PEG?
Polyethylene glycol, or PEG, is a polymer that is nontoxic, nonimmunogenic, highly water soluble, and readily cleared from the body. PEG has many different applications and is commonly used in foods, cosmetics, beverages, and prescription medicines. Pharmaceutical grade PEGs are approved for use in the United States by the FDA and are widely used as biopharmaceutical carriers, given their high degree of biocompatibility.

Why attach PEG to biopharmaceuticals?
Prolong Pharmaceuticals creates improved, high-value biopharmaceuticals utilizing its extensive knowledge and practical expertise in the field of PEGylation. PEGylation is the process of attaching one or more chains of PEG to a protein molecule, thus creating a PEG-conjugated protein. PEGylation can modify certain characteristics of biopharmaceuticals without altering their function, thereby enhancing the therapeutic effect. PEG can be coupled to active biopharmaceuticals through the hydroxyl groups at the ends of the chain using a variety of chemical methods. The benefits of PEGylation to a known protein-based biopharmaceutical (compared to a non-PEGylated version) include:

1. Improved pharmacokinetics
   • enhanced solubility
   • improved stability
   • sustained absorption
   • continuous biopharmaceutical action
2. Increased circulation time
   • decreases amount of protein required for therapeutic efficacy
   • decreases dosing frequency due to optimized biodistribution
   • reduced renal clearance increases circulation time
3. Decreased toxicity
   • Improved safety profile
   • reduced immunogenicity
   • reduced antigenicity
   • reduced proteolysis

These benefits allow significantly less protein (as compared with the unmodified protein) to be administered to patients and yet achieve the same desired therapeutic effect while using a decreased dosing schedule. In addition, a reduction in the amount of protein used in each dose results in lower raw material and production costs.