[Ip-health] MSF’s pneumonia vaccine patent challenge and its implications- A changing ecosystem for Indian pharma?

leena menghaney leenamenghaney at gmail.com
Tue Mar 29 01:46:27 PDT 2016

MSF’s pneumonia vaccine patent challenge and its implications- A changing
ecosystem for Indian pharma?
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In this post  Swati Muthukumar, Spicy IP Fellowship applicant discusses
MSF’s challenge to Pfizer’s pneumococcal conjugate vaccine in India. Swati
is in her fifth year at NLS, Bangalore. This is her first submission for
the fellowship.

This March, Doctors Without Borders (MSF) took an important stance against
the large pharma manufacturer Pfizer by making a pre-grant opposition to
their pneumonia vaccine patent, Prevnar 13. Prevnar 13 is a vaccine
essential in ensuring the immunization of children worldwide against
Streptococcus pneumoniae, the bacteria which causes pneumonia and occurs in
different strains throughout the world. Prevnar13 is one of two vaccines
available (the other being GlaxoKline’s SynFlorix)  for such immunisations
and both are extremely expensive, costing Rs. 3800 and Rs. 1800 per dose
respectively. MSF says that the high price can be brought down by bringing
in national competitors to the market, stating the example of the Hepatitis
B vaccine, whose restrictive pricing was changed dramatically with the
entry of Indian manufacturers not having to face patent barriers. Following
their negotiations with Pfizer to reduce the price, they have challenged
the patent application 8081/DELNP/2007 on March 11, 2016.

Arguments in MSF’s Opposition

In their opposition, MSF has stated that the patent application lacks
novelty, does not possess an inventive step, does not constitute a
patentable ‘invention’ and lacks specificity in explaining the processes
involved in its application.

The patent application is for a ‘multivalent immunogenic compound,
comprising: 13 distinct polysaccharide protein conjugates  together with a
physiologically acceptable vehicle, wherein each of the conjugates
comprises a capsular polysaccharide from a different serotype conjugated to
a carrier protein, CRM197 and are prepared from Streptococcus pneumonia
serotypes 1,3,4,5,6A,6B,7F,9B, 14, 18C, 19F, 23F.’ This innovation uses a
carrier protein CRM197 with an aluminium based adjuvant.

In other words, pneumococcal vaccines in order to target different strains
of the pneumonia bacteria contain different strains, or serotypes in their
conjugate. This pneumococcal conjugate vaccine has 13 serotypes, or is a
tri-decavalent vaccine (PCV 13). In order to increase the efficacy of the
vaccine, studies found that the use of a conjugate with a carrier protein
was beneficial and has been adopted here. MSF’s arguments are as follows:

Lack of Novelty under S. 25(1)(b) and (c) of the Patents Act: The knowledge
of serotypes in various regions, the efficacy of the use of a detoxified
bacterial toxin protein such as CRM197 and the manufacture of multivalent
vaccines such as 7-valent Prevenar is already known. The specification here
merely makes an addition of 6 more serotypes, which are also known in prior
art. Other prior art bearing near exact similarity has been discussed in
great detail, namely GlaxoSmithKline’s S. Pneumoniae vaccines WO
2003/051392 and WO 2000/056359, which additionally use an aluminium

Lack of Inventive Step under S. 25(1)(e): The claims are obvious through
the disclosure of prior art, with immunogenic polysaccharide protein
conjugates known since the 1980s for immunization of infants (US 4902506
discusses this S. Pneumoniae conjugated with CRM197 and the use of several
serotypes). US 5623057 of 1997 discloses a capsular polysaccharide vaccine
from different serotypes of S. Pneumoniae. The use of multivalent vaccines
for pneumococcal diseases has been disclosed in several publications before
the 2000s and has been discussed in detail by the opposition, including the
use of 13-valent composition. Further, based on existing knowledge a
skilled person through prior art would consider the use of polysaccharides
conjugated to a carrier protein and an additive of aluminium phosphate as
lacking an inventive step.

Not an ‘Invention’ under S.25(1)(f): Since the claims are not novel,
inventive and lack industrial application as previously indicated,  the
patent cannot be granted. Further, it is argued that components (comprising
a serotype carrier proteins and an adjuvant) all act individually and not
in manner exhibiting synergy. Thus they are not eligible for a patent under
S. 3(e), as they form ‘a mere admixture resulting only in the aggregation
of the properties of the components thereof or a process for producing such
substance’. Further, as the vaccine is a mode of treatment of human beings,
under S. 3(i) it should not be eligible for a patent.

Lack of Adequate Description under S.25(1)(g): The description contained in
the patent application does not adequately list out the novelty of addition
of serotypes, any technical solutions through their specification nor the
utility of the vaccine. The composition is vague and does not provide the
range or value of components, the effect of adding the adjuvant, etc.

Failure to disclose information under S. 25(1)(h):  The Applicant was
required to disclose in their application and to the Controller (as per S.
8) all foreign applications and their status. Many of these applications
have been cancelled and the failure to disclose this should result in
rejection of the claim.

Considering the European revocation

>From the above opposition, it is apparent that there are a number of
grounds under which MSF is questioning the PCV13 patent. To an extent, we
can evaluate the veracity of an opposition by considering the decision of
the Opposition Division of the European Patent Court regarding the same
patent. In the case of this particular vaccine, there is no doubt that the
revocation of Pfizer’s patent by the European Patent Office provides a
strong indication of the invalidity of the application. In 2014, the
European Patent Office considered a total of five oppositions considered
before the Opposition Division and on appeal, upheld this decision. The
Opposition Division in this case held that the patent was revoked on
grounds of lacking inventive step on the following points-

D36, a review article which proposes that a 13-valent vaccine is being
studied and the serotypes to be used were discussed. It also refers in
detail to the conjugate 7 and 9 valent vaccines, which are both conjugated
to CRM197. The Opposition Division thus held that the patent did not have
an inventive step as a skilled person would be able to produce a 13 valent
vaccine based on D36a proposed serotypes, coupled with CRM197 and
saccharides based on pre-existing methods.
 The patent-holder argued that prior art teaches away from the use of an
aluminium adjuvant, however the Opposition Division referred to prior art
D35 which discloses use of aluminium phosphate and saccharide amount having
a 10% difference from those in the current patent. The European Patent
Court thus found the patent did not meet the standards of the court and
revoked it. Yet we find that generic manufacturers are not involved in
opposing the same.
The use of a sodium chloride and sodium succinate buffer were seen to be
commonly used vaccine components and did not act in any unique manner in
this particular application.

We find that the lack of inventive step analysis can be further applied by
Indian courts as well, with a similar conclusion that a skilled person
would be able to arrive at the patent through mere analysis of prior art.
The patent is also being challenged in South Korea and the effect of this
opposition is yet to be seen. At this stage, however, it is important to
look into the broader issue of what the opposition means for the Indian
patent law and the pharma market.

The Future of the Indian Pharma Ecosystem

So why did MSF oppose the patent application in India? India is an
important manufacturer of generic drugs and pharma that supplies a majority
of the vaccines used by UNICEF. UNICEF additionally foresees in their
Supply and Demand Update a substantial rise in dosage required by them,
which currently must be met entirely by the two existing manufacturers and
is phased out in terms of priority in the event that there are insufficient
vaccines available. Additional manufacturers will definitely assist in a
more quick and efficient vaccination process worldwide. Even in the present
case, MSF states that an Indian manufacturer has already stated that he can
provide all three doses of the pneumonia vaccine at the cost of $6 per
child (approx. Rs. 400), which is substantially lower than the present
rates.  The legal position in India can thus have an international impact
on drug and vaccine supply, and in the case of pneumococcal vaccines, it
can be a game changer in terms of price range and quantities.

Lack of patent oppositions by generic manufacturers: Shailly Gupta, the
deputy head of MSF Access has highlighted the effect of the changing
atmosphere in patent law with respect to generic manufacturing in India,
following the judicial system being more willing to stay such manufacturing:

“‘…Courts have started granting stays, and the now generic companies no
longer want to challenge originator companies holding patents”, said Gupta.
Despite Make in India, she said, Indian generic firms no longer feel they
can work in this atmosphere. Many have started tying up with originator
companies, letting them fix the price, leading to fears of impacts on
patients when pharmacies only have expensive drugs to offer.’

The result of this licensing regime is that the price of such generic drugs
may increase substantially, potentially making it as unaffordable as the
drug or vaccine produced by the original company. More importantly,
oppositions to patents in big pharma are becoming less common, allowing for
non-meritorious patent applications to go unopposed, unless, of course,
organisations such as MSF (with an interest in accessible medicines and
vaccines) step in.

Is compulsory licensing a possible alternative in this case? India has in
the past granted compulsory licenses at times when the need to ensure
public access to the drug is seen as overriding the need to protect the
monopoly holder’s patent. In the event that the challenge to the patent
application fails, a compulsory license could ensure continuing competition
in the market and increased access to medical aid, albeit with a less
dramatic price reduction. However, if there is indeed a ‘chilling effect’
on generic manufacturers, as stated by MSF, which is causing them to avoid
engaging with or potentially antagonising patent originators except to tie
up with them, this could pose some concerns.

The larger issue of course is that it is increasingly becoming the role of
civil society at large to ensure that big pharma patents are opposed, so
that the market and the resulting access to affordable medical aid is not
unduly and wrongfully restricted. As the public does not always possess the
skilled knowledge or resources to do so, one would hope that the government
recognizes the practical loophole in pharma patents today and take steps to
address it.

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Leena Menghaney
Mobile: 9811365412

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