Human Genome Sciences acquires Principia Pharmaceutical
Principia focused on extending half-life of proteins and peptides
Human Genome Sciences Inc. (HGS; Rockville, MD) has acquired privately-held Principia Pharmaceutical Corp. (Norristown, PA), whose specialty is peptide and protein drugs for serious chronic diseases.
Principia's technologies are aimed at the short biological half-life of peptide and protein drugs, disadvantages that mandate high doses and frequent injections. Principia's recombinant albumin fusion technology provides longer-acting forms of many important biopharmaceuticals by genetically fusing the therapeutic protein to albumin. When fused to therapeutically active proteins, the active protein conjugates appear to have about the same circulating life as albumin, potentially leading to reduced dosing frequency and fewer side effects.
In addition to therapeutic benefits to albumin conjugation, HGS is also banking on a manufacturing advantage. Fusing a therapeutic protein to the large albumin molecule could reduce recovery and purification steps. Typically, engineers must design an individual purification protocol for new proteins and peptides. All albumin-fused proteins, however, will share the albumin component, which may lead to standardized purification steps.
Genetic, not Chemical Conjugation
Creating fusion proteins involves fusing albumin DNA with the DNA for a therapeutic protein or peptide. This fused DNA then signals to produce the albumin fusion protein directly from yeast expression systems.
It turns out that Albumin is the ideal carrier protein because its abundance in plasma (40g/liter) makes it inefficient for the body to turn it over as frequently as it does other proteins.
Physical and chemical tests to date have shown that fusion proteins are folded correctly to do the job of the "guest" protein or peptide. Tryptic mapping under non-reducing conditions generates peptides that confirm correct three dimensional disulfide bridging. Also, high solubility, stability, and activity are indicators of a correctly refolded molecule.
For more information: Human Genome Sciences Inc., 9410 Key West Ave., Rockville, MD 20850-3338. Tel: 301-309-8504. Fax: 301-309-8512.
Edited by Angelo DePalma
Managing Editor, Drug Discovery Online