A recent study has shown that the active ingredient in Viagra (sildenafil) has the capacity to slow the spread of malaria parasites.  The study provides a timely reminder of the relevance of ‘second medical use’ patents and their potential for extending the period in which a substance/composition can be patent protected.

Blocking parasite transmission with sildenafil

Malaria is a life-threatening disease caused by blood-borne parasites that are transmitted to people through the bites of infected mosquitoes.  As reported by the World Health Organisation, malaria remains a significant global problem given that it impacts approximately 200 million people per year.  As a former researcher, I contributed to the development of vaccines that aimed to combat the severity of Malaria understanding full well the impact of the disease, particularly in African children.

The study, published recently in the journal PLOS Pathogens, examines the transmissibility of malaria parasites.  In particular, the authors observe that parasite-infected red bloods cells are deformable and have the ability to circulate relatively freely through the body whereas non-deformable infected blood cells can potentially be trapped and cleared via the spleen (the body’s blood filter).  Deformable infected blood cells, having escaped the spleen, can be taken up and transmitted by mosquitoes after feeding on an infected individual.

The authors determine that a parasite-derived enzyme (cAMP-dependent kinase A) has the ability modulate the stiffness of membranes of infected red blood cells.  Blocking this enzyme with known kinase inhibitors, or engineering recombinant parasites having decreased expression of the enzyme, decreases the stiffness of infected red blood cell membranes.  This, in turn, increases the ability of the parasite-infected cells to escape the spleen.  Thus, an increased deformability correlates with reduced enzyme activity and a decrease in red blood cell cAMP levels.

Sildenafil is a known phosphodiesterase inhibitor which particularly targets phosphodiesterases that breakdown cAMP.  Thus, treatment with sildenafil results in increased intracellular cAMP levels.  In exploiting this known property, the authors treated infected red blood cells with sildenafil and found that the treatment decreased deformability.  This would therefore increase the chance for clearance of infected cells by the spleen.

In practice, treating parasite-infected individuals with sildenafil may be impractical given the unintended side-effects.  Further, the treatment would not cure those already infected.  Nevertheless, the study provides ‘proof of principal’ support for the development of new drugs that have the capacity to block malaria parasite transmission by increasing intracellular cAMP levels.  Such drugs are likely to form a part of a multifaceted approach for combatting malaria.

Could the use of sildenafil in treating malaria be patentable?

A well understood principle provided by patent law in most jurisdictions is that, where a substance or composition is patented in respect of a ‘first medical use’, it may still be patentable for a ‘second medical use’, provided that the second use is novel and inventive.

Sildenafil is, itself, a great example of a compound having a ‘second medical use’.  The drug was originally developed in the late 1980‘s by Pfizer for treating cardiovascular diseases and conditions, primarily hypertension.  In clinical trials, it was found that the drug had the unintended effect of causing penile erections in male volunteers.  This led Pfizer to patent sildenafil for treating male erectile dysfunction (ie. a ‘second medical use’).

Now it might be the case that another patent application has been filed directed to this new indication in treating malaria.  However, the assessment of patentability can be complicated.  Without conducting extensive searching or analysis, it would be difficult to confidently conclude that the use of sildenafil for the preventing malaria transmission could be patentable based on the results of the above study alone.  The fact that the abovementioned authors have exploited a known property of sildenafil (ie. its use in increasing cAMP levels) will at least increase the inventive step hurdle that would need to be overcome before a granted patent for this second medical use could be obtained.

Meeting disclosure requirements for second medical use patents in Australia and New Zealand

In Australia, first and second medical use claims, method of medical treatment claims, and Swiss-style claims (which protect against illegitimate manufacture of a substance/composition as opposed to the substance/composition per se) are patent eligible.  In New Zealand, first and second medical use claims and Swiss-style claims are patent eligible, but method of medical treatment claims are not.

In Australia, under the previous version of the Patents Act 1990, Pfizer’s patent for the use of sildenafil in treating erectile dysfunction was challenged on the basis that the patent specification did not sufficiently disclose the best method for treating erectile dysfunction at the time of filing.  In fact, the best method was introduced into the specification by way of amendment (in the form of a claim directed to the active sildenafil monocitrate) approximately three years after the corresponding application was filed.

The point here is that the ‘Raising the Bar’ amendments to the Patents Act 1990 increase the disclosure requirements for Australian patent applications while restricting the types of amendments that can be made after the application is filed.  Among other things, the threshold for claim support has increased, thus reducing the likelihood of obtaining unduly broad patent protection based on a general description of the invention with little or no exemplification.  A similarly increased support requirement is now prescribed by the newly amended New Zealand Patents Act 2013.

In short, a patent specification directed to the second medical use of a substance/composition, if drafted to have a full and complete disclosure should satisfy the higher threshold support requirements of the amended Australian and New Zealand Patents Acts.  A properly drafted specification that meets these standards should also meet the standards of major foreign jurisdictions, such as the US and Europe and can be a critical tool for returning investment on the initial development of the substance/composition.

Is there commercial value in ‘second medical use’ patents?

While it is sometimes difficult to estimate the commercial value of ‘second medical use’ patents, the sildenafil example shows that protection for a second medical use can be of great significance in extending the commercial life of a patented drug to generate valuable returns.

However, obtaining a patent directed to a ‘second medical use’ of a known compound/composition won’t necessarily prevent generics manufacturers from entering the market with products specific for the previously patented ‘first medical use’, and the misprescription of generic drugs for the patented ‘second medical use’.  We have previously reported on the reality of misprescribed generics for patented indications.  Thus, from a commercial perspective, the benefit in obtaining a patent directed to a ‘second medical use’ of a known compound/composition must be weighed against the diminished returns as a consequence of operating in market flooded with misprescribed generics.