As science gets better at unravelling the mechanisms of action that underpin biological therapeutics, there is growing interest in finding new uses for established protein molecules.
New indications can be an efficient way to access lucrative markets with existing products. Established biological medicines benefit from safety and tolerance profiles that are already well known to regulators and physicians. There are nearly one thousand FDA and EMA-regulated biologics to choose from and new indications can extend patent protection by up to 20 years. Assuming the molecule patents have expired, businesses are spared the cost of in-licensing.
There are drawbacks however. The biggest problems associated with switching indications relate to manufacturing complications and so-called ‘patent thickets’.
For regulatory reasons, existing manufacturing methods are sometimes patent protected for up to 20 years. This can lock in inefficient manufacturing processes that might not be suited to the new market, creating a range of technical difficulties.
For example, expensive downstream processing steps are required if additional molecular groups need to be removed from the secreted protein. Toxins and impurities caused by an existing upstream manufacturing process might also need to be addressed in the same way.
Sometimes new indications that involve more frequent or higher dosing than the original therapeutic applications will require larger volumes of plant. Depending on the net yield of the existing manufacturing method, more up-front capital expenditure might be needed, potentially reducing gross margins at scale to the point where it’s no longer competitive. In some cases the original manufacturer retains technical know-how which can create additional challenges.
Biologics are often surrounded by a patent ‘thicket’, in other words a large number of patents that are designed to provide additional layers of protection for the product and extend the duration of cover. The majority of patents in these thickets usually relate to processing. Patent filing dates can be deliberately staggered to extend their effective monopoly. So while the headline composition of matter patent might be clear and in line with the development timescale – the devil is in the detail.
Having navigated the patent thicket, your next challenge is to police your new patent estate. This is more of a practical problem. In theory your use patents create a monopoly for the biologic. In reality it will remain on the market for its original indications. Physicians can be tempted to prescribe it ‘off label’ for the new indications given the price of the product for the original indication is likely to drop due to biosimilar competition. The original manufacturers and their biosimilar competitors are not allowed to promote your labelling for their product but they are unlikely to make much of an effort to discourage ‘off-label’ use.
Existing solutions are limited
Contract manufacturing organisations (CMO), contract development manufacturing organisations (CDMO) and specialist consultants can offer their expertise to tackle some of the technical issues associated with indication switching. But their reliance on established manufacturing methodologies does not allow for multi-parameter optimisation, which can be the deciding factor that turns a stalled project into a compelling commercial proposition.
Resurrecting new indication projects with QTL
Quantitative Trait Loci (QTL) technology has the potential to resurrect indication switch projects and unlock fresh value from a range of low cost assets. It introduces genuine multi-parameter optimisation to recombinant protein manufacture for the first time, harnessing the full power of biology to overcome barriers that often stall new indication projects or make them unviable.
QTL technology creates and customises premium recombinant proteins that are patent protected and designed to dominate your market in the following ways:
- Creating optimised manufacturing strains that create the protein or peptide required while reducing or removing costly downstream processing requirements.
- Improving headline titre and post processing net yield to significantly reduce the scale of manufacturing plant required and substantially lower commercial scale cost of goods.
- Providing a patented strain to expand and strengthen the patent protection of the product.
- Providing a basis of genetic tagging that identifies the proteins or peptides manufactured by the optimised strains, to assist in proving patent breaches and policing new indication patents.