Patent evergreening in the pharmaceutical industry: How
inventive are new crystal forms?
Pharmaceutical companies typically invest substantial amounts of
money into research and development. Their research, however, is
not only aimed at discovering new active pharmaceutical ingredients
(APIs). Instead, some companies make small modifications to
existing APIs to enhance their effectiveness, manufacturing or
processing. These modifications are used to obtain secondary
patents which in effect extend the 20 year life of the original
patent. In addition, most countries have strict rules pertaining to
generic medicines. If the generic medicine does not have the same
chemical structure and bioavailability as the original product it
cannot be registered and sold. The secondary patents often prevent
generic products being registered and the practice of filing these
has been termed patent "evergreening".
Numerous patent cases have been fought over the patentability of
new crystalline forms of APIs. A different arrangement of molecules
in a single crystal, which is obtained when different processing or
crystallisation methods are used, can result in a new crystalline
form. A new crystalline form of an API may be superior to existing
or "prior art" crystalline forms by virtue of it having
enhanced solubility, ease of formulation or stability. In some
cases, its therapeutic efficacy may also be enhanced. Patentability
disputes generally revolve around the novelty and inventiveness of
a new crystalline form. However, what is considered inventive may
vary from country to country.
India has adopted what appears to be a strict policy against
patent evergreening, seen by some as an attempt to support its
enormous generic pharmaceutical manufacturing industry. According
to section 3(d) of the Indian Patents Act, a new crystalline form
can only be patented if its therapeutic efficacy is significantly
enhanced over existing crystalline forms. In a high-profile case, a patent for a new
crystalline form of the cancer drug Gleevec was denied to Novartis
in April 2013. Novartis provided evidence that the new
crystalline form has improved flow properties, improved stability
and lower hygroscopicity than existing forms. However, the courts
there found that these improvements did not satisfy the
requirements of section 3 (d) in that there was no evidence of the
new crystalline form having a significantly improved therapeutic
efficacy. The precedent set by this judgement has been noted with
interest in South Africa and other developing nations where
healthcare is not accessible to large sections of the population
and where patents are seen as entrenching monopolies and
unaffordable high prices.
In the United Kingdom, the pharmaceutical company Les
Laboratoires Servier attempted to obtain an interim injunction
against the generic pharmaceutical company Apotex to prevent it
from selling the block-buster drug perindopril. Servier's
original patent for perindopril (Coversyl®) had expired, but in
the years preceding expiry, Servier had filed numerous further
patents, including a patent for a "new" crystalline form
(the "α form") of perindopril. The UK
trial took place in 2007 and it was found that the patent was
invalid. Evidence showed that the α form was always
produced, including in the process originally patented by Servier
(European Patent No. 0,308,341). The Court of Appeal was scathing
in its remarks on the patent, finding that "it is invalid.
And very plainly so. It is the sort of patent which can give the
patent system a bad name. ...The only solution to
this type of undesirable patent is a rapid and efficient method for
obtaining its revocation. Then it can be got rid of before it does
too much harm to the public interest."
Servier similarly tried to prevent South African generic
companies Cipla Medpro (Pty) Ltd and Ranbaxy (Pty) Ltd from
entering the market with perindopril. However, after this matter
appears to have later been settled out of court.
In the perindopril cases, extensive evidence was adduced by the
generic pharmaceutical companies showing that the α
form was not new. This type of evidence is expensive and
time-consuming to produce as it requires the input of various
experts in the field and may even require further expert research
and experimentation to prove the invalidity of a novel crystal form
that forms the basis of a secondary patent. This is a major reason
preventing more litigation around new crystal forms. What is needed
are more specific and clear guidelines and much can possibly be
learnt from India in this respect.
It has always been the practice of the Industrial Property Institute of Mozambique to prohibit the refiling of trade marks that have been finally refused, which has posed a serious obstacle to trade mark applicants...
As reported in the market updates section of this newsletter, the UAE Ministry of Economy recently reviewed the fees charged by its various departments, including the Trade Mark, Patent and Copyright Office.
Managers responsible for ensuring that an organisation’s intellectual property rights are protected often believe that the organisation automatically owns all intellectual property rights arising from the work of its employees.
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