Patent

I-MAK files pre-grant opposition against Gilead’s antiviral drug Sofosbuvir


Non-profit group I-MAK (Initiative for medicines access and knowledge) filed a pre-grant opposition last week at the Indian patent office against Gilead’s  Sofosbuvir, potential blockbuster drug used to treat Hepatitis.Sofosbuvir has received an unprecedented  unanimous approval from the FDA advisory panel last month. Anticipating its launch in India, I-MAK filed a pre-grant opposition against the prodrug patent.

Background and Factual matrix

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Sofosbuvir (PSI-7977), a nucleotide analogue was developed at Pharmasset Inc., which was subsequently acquired by Gilead Sciences. Sofusbuvir has been touted as a potential game changer in Hepatitis C therapy, since it’s the first of its kind all oral treatment for Hep C genotypes 2 and 3 thus completely obviating the need for grueling injectable interferon and avoiding needle stick injuries and other unpleasant side effects.

Patent status

A cursory patent check reveals that Sofosbuvir is protected by two patents that claim Sofosbuvir as a chemical entity and its metabolites.

PCT application WO2005/003147 (US7429572) claims metabolites of sofosbuvir i.e. covers the parent structure of sofosbuvir minus the prodrug (2’R)-2′-deoxy-2′-flouro-2′-C-methyl nucleoside (β-D or β-L),and also claims prodrug of sofosbuvir, and the use of  such compounds for the treatment Hepatitis C virus and expires on 21st April 2024. This probably corresponds to Indian patent application 2079/DELNP/2011.

Indian patent application no. 3658/KOLNP/2009 (corresponds to US7964580) stems from PCT application WO2008/121634 and claims nucleoside phosphoramidate prodrug of sofosbuvir. This patent is what you would call as a “secondary patent” and expires on 26 March 2028.

 It is interesting to note that Sofosbuvir is a prodrug that is metabolized to the active antiviral agent as claimed in PCT application WO2005/003147.

Grounds of Pregrant opposition

I-MAK has filed a pre-grant opposition against Gilead’s Indian patent application no. 3658/KOLNP/2009 on the grounds of lack of novelty Section 25 (1)(b), obviousness Section 25(1)(e), Section 3(d) and failure to furnish Section 8 details. The entire text of the pre-grant opposition filed by I-MAK can be accessed here. The grounds of opposition are discussed below.

Lack of novelty: The earlier patent i.e. WO2005/003147 discloses both the parent structure of sofosbuvir and also the stabilized phosphate prodrug form. So the ‘147 patent anticipates the later prodrug patent.

Obviousness: The opposition text cites various prior arts and states that the prodrug (pro-tide) strategy which improves the pharmacokinetic characteristics of the parent compounds is a well-known one. Thus it would have been obvious for a person skilled in the art to pursue the phosphoramidate prodrug approach for sofosbuvir.

Section 3(d): new form of a known substance that does not result in an enhancement of the known efficacy of the known form; to meet the requirements of Section 3(d), it is necessary to show that the prodrug form enhances the therapeutic efficacy of the already known form. However the applicant has not included any comparative data in the 3658’ application. The Supreme Court in the recent Novartis case ruled that an increased bioavailability alone may not necessarily lead to an enhancement of therapeutic efficacy.

So in this case if the applicant were to amend the specification and include additional comparative data, the threshold question would be whether an increase in bioavailability provided by the nucleoside phosphoramidate prodrug would lead to an enhancement of therapeutic efficacy of the known form. In this context, to get a clearer picture of Supreme Court’s interpretation of Section 3(d) read Prashant’s analysis here. The finer aspects of how Section 3(d) and efficacy should be construed are detailed in Shamnad and Prashant’s article here.

Pricing conundrum?

Federal-Drug-Prices-in-VA-and-DoD

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According to this Forbes story by Ed Silverman Sofosbuvir is expected to be priced at $80,000 -90,000$  per patient. The Forbes story also highlights that production cost of Sofosbuvir can be as little as at $68 to $136 for a 400 mg dose for 12 weeks. The price disparity is apparent!

Of course production costs are not the only costs which determine price of a drug, the clinical trials for FDA approval and R&D costs must also be taken into consideration. Additionally,the duration of treatment also gives little reason for drug companies to lower costs because unlike anti-retroviral therapies which must be taken for a patient’s lifetime, HCV treatment is given for only 12 weeks. Interesting statistics regarding the no of HCV affected people; cost of manufacturing and pricing of sofosbuvir is available here.

Conclusion

Even if I-MAK were to prevail and the prodrug patent is refused, the patent which claims the parent structure of sofosbuvir 2079/DELNP/2011 (corresponding to WO 2005/003147) expiring in 2024 would be the one to watch out for. The Indian patent application 2079/DELNP/2011 is awaiting examination, but details of claims and specification are unavailable.

Regarding the pricing strategy, GSK CEO Andrew Witty backed India’s policies on patents and pricing and in this Economic times article he aptly states “If we have to find a way of bringing innovation to India, you should have prices which are affordable “And the key to that isn’t to get rid of patents. The key to that is to fix the R&D process; the manufacturing process to make it more efficient.Companies cannot turn up and have any price they want. Companies have to come up with a competitive and efficient business model.” And I couldn’t agree more!

 

 

Madhulika Vishwanathan

Madhulika Vishwanathan

Madhulika is a registered Indian patent agent and has completed her Master’s in Pharmacology from the Institute of Chemical Technology (ICT), Mumbai. Her interests include issues involving pharmaceutical and biotechnology patent law, regulatory aspects like Hatch Waxman litigation and antitrust law.She is currently working at law firm based out of Memphis, TN.

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