Novozymes, Upperton move nanoparticles towards commercialisation

The new agreement focuses on the commercial exploitation of the companies' jointly owned rP-nano technology, which Upperton will use to generate nanoparticles from recombinant proteins expressed in Novozymes' proprietary yeast-based system. The rP-nano technology can produce nanoparticles from all types of peptides and proteins, including monoclonal antibodies and enzymes, without denaturation. Its suitability for pharmaceutical applications will be demonstrated to potential licensees using nanoparticles generated from recombinant human albumin. Novozymes manufactures Recombumin, the only animal-free commercially available recombinant human albumin approved by both the European Medicines Agency and the US Food and Drug Administration for use in the manufacture of human therapeutics. As part of their collaborative programme, Novozymes and Upperton demonstrated proof of principle with rP-nano using recombinant human albumin and recombinant transferrin manufactured by Novozymes. In one study, nanoparticles generated from recombinant human albumin were loaded with monoclonal antibodies, radioactive metal ions, chemotherapy agents and paramagnetic metal ions. Under their extended partnership, the two companies will seek out academic or industrial partners who can further develop the technology in a range of clinical applications. The current focus is on drug and gene delivery - for example, cancer therapeutics, vaccines, DNA/iRNA, pulmonary delivery or localised delivery for wound-healing/topical applications. The scope could also extent to in vitro​ diagnostics and personal care products. As rP-nano is jointly owned and co-patented, any milestone payments and royalties on future sales from licensing of the technology will be split equally between Novozymes and Upperton. Novozymes says it is too early at present to estimate the market potential of any rP-nano applications. Given its "extensive know-how in producing nanoparticles from biomolecules and loading them with drugs and other substances"​, Upperton will provide technical support to licensees on a fee-for-service basis, Novozymes notes, adding that Upperton will "primarily seek funding from potential licensees to show feasibility across a number of applications"​. Novozymes will also benefit from sales to licensees of recombinant human albumin and transferrin for the manufacture of recombinant protein nanoparticles using the rP-nano system. As the company points out, the successful uptake of nanoparticles across membranes and cell surfaces depends on controlling and optimising particle size. The rP-nano system can generate precisely-sized nanoparticles within the range of 10nm to 120mn. These particles can then be optimised for enhanced permeability and retention. They are also highly stable and amenable to freeze-drying, adds Upperton. Moreover, the manufacturing process is "very robust, stable and reproducible"​, with a single-phase reaction for particle formation. Size distribution can easily be varied through straightforward changes to reaction conditions. Other cited advantages are that no detergent or organic solvent are required in the manufacturing process, the particles do not contain any extraneous chemicals, and the process is easily scaled up. The manufactured nanoparticles can then be "efficiently and densely​" loaded with drugs or other substances such as antibodies, antigens, enzymes, DNA or RNA. Upperton says it has also developed a proprietary method for loading albumin nanoparticles with monoclonal antibodies while "fully preserving antibody activity​". The loaded nanoparticles retain the natural binding properties of the recombinant proteins they are made from, with the capacity to bind to specific cell types and enhance both compound targeting and bioavailability. The potential benefits for patients, Novozymes observes, are improved efficacy of pharmacological agents, reduced side-effects through better targeting, and management of healthcare costs by reducing the amounts of active protein needed, as well as the frequency of administration. Competing technologies include serum albumin nanoparticles used to deliver anticancers, such as Abraxis BioScience's Abraxane (paclitaxel protein-bound particles for injectable suspension) - already on the market in the US and Europe. Novozymes also cites the polyglutamate-based soluble polymers (Genetic Polymers, licensed from Cell Therapeutics) under development by Aequus Biopharma for extending the plasma half-life of peptide- or protein-based biopharmaceuticals. But none of these technologies have the key features exhibited by the rP-nano system, Novozymes claims. The closest match to rP-nano is the nab platform used with Abraxane, which consists of human serum albumin nanoparticles produced as an emulsion. According to Novozymes, though, rP-nano has "a number of key competitive advantages​" over the nab technology. These include sensitive control of particle size; retention of all proteins in their active forms (i.e., no denaturation); the use of animal-free recombinant proteins to generate the particles, which "not only improves safety but also enhances product acceptance by the regulatory authorities​"; and applicability to all water-soluble compounds. Founded in 1999 and based in Nottingham, UK, Upperton is a privately owned biotechnology company that specialises in spray drying and particle technologies. It said the breakthrough to a next-generation technology for generating nanoparticles from proteins followed "more than seven years of dedicated research​" in collaboration with Novozymes Biopharma UK, the business unit formed through Novozymes' acquisition of Delta Biotechnology in July 2006.