Research by its nature can be inexact, and a serendipitous discovery made during a research programme may be of greater value than the result initially intended. In the pharmaceutical industry there are many instances where a chance observation or ‘side effect’ observed during clinical trials has led to a commercially important product.
The ability of an organisation to recognise these opportunities and take advantage of them can turn a failed research project into a significant revenue stream. This requires not only the ability of the organisation to recognise the potential commercial applications of any observed ‘side effect’, but also requires astute use of the patent system to ensure that second generation patents are filed to protect the commercially important new application.
The Sildenafil story
In 1991, Pfizer researchers were working on compounds for the treatment of hypertension, and were particularly interested in pyrazolopyrimidones. They synthesised a number of compounds in this class including UK-92,480 (the number given to sildenafil), and subsequently filed a patent application covering the compounds and their use in the treatment of cardiovascular disease in 1992.
As luck would have it, during clinical trials it was found that the drug had little or none of the desired effects and was therefore found to be ineffective for the treatment of angina (the initial purpose of the drug). They did, however, notice a side effect that the drug could improve and sustain a man’s penile erection. In what was surely an example of amazing flexibility in the decision making tree for a company of that size, Pfizer almost immediately stopped research into the use of sildenafil as a heart medication, and initiated investigations into its use in the area of male erectile dysfunction. As a result of this research, Pfizer filed a second patent application directed towards the use of sildenafil to treat erectile dysfunction in 1994. This was clearly a success for the company given that sales of Viagra ranged between 1.5 US billion and 2.1 US billion per annum for each year from 2003 until 2014.
The Minoxidil story
Minoxidil was first developed by the Upjohn Company in the late 1950’s, and was intended to be used for the treatment of ulcers. Unfortunately the drug was found to be relatively ineffective as a cure for that condition, but was found in 1965 to be an effective vasodilator that could be used as a treatment for hypertension. The company obtained a patent for the drug in 1967 and received market approval in 1979. The drug was then marketed under the trade name Loniten for the treatment of hypertension.
During the clinical trials into Minoxidil, clinicians observed unexpected hair growth on the faces and shoulders of some subjects, and some men reported hair regrowth on their heads. As a result of the observation, a second patent application was filed in 1971 directed towards hair regrowth using Minoxidil. The sales of the active agent under the trade mark Rogaine turned into a significant income earner for the company, complementing sales of the compound as a hypertensive.
The Bimatoprost story
Bimatoprost was first developed to lower intraocular pressure in patients suffering from chronic glaucoma or ocular hypertension, and patent applications were first filed covering the molecule in 1992. In 2001, approval was given by the FDA for its use in lowering intraocular pressure and the drug entered the market.
During clinical trials it was observed that patients treated with the drug noticed an increase in diameter, density and length of eyelashes. As a result of this observation, in 2002, Allergan filed patent applications directed towards the use of the compound to treat hair loss, and in particular for stimulating eyelash growth. Allergan were able to obtain patents and subsequent regulatory approval for the cosmetic use of darkening and lengthening eyelashes and the active agent is now sold under the trade name Latisse. Given the number of potential users of the active agent for cosmetic purposes far outnumber the patients who need to be treated for high intraocular pressure, this observation has significantly increased the sale potential of this drug for the company.
In addition, the second generation patent directed towards the cosmetic use will expire almost 10 years after the original molecule patent. The net effect of this is that Allergan will be able to derive a significant income stream from their original research long after the expiry of the original compound patent.
As illustrated by these case studies, quite often a research project does not provide the original desired results, and the initial patented use of a compound may not turn out to be a successful commercial product. Nevertheless, diligent observation of patients during the clinical trial phase may reveal ‘side effects’ that can be turned into very successful products, which in some instances may be more valuable than those the initial research was intended to provide.