Spicy IP Fellowship 2016-17: MSF’s pneumonia vaccine patent challenge and its implications- A changing ecosystem for Indian pharma?

In this post  Swati Muthukumar, our 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 adjuvant.

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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