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The struggle between innovator pharmaceutical companies (mostly in the Western world) and developing world Generic companies have been lately played out in India and especially for the last 2-3 years in the form of litigations and oppositions. Here I would be discussing the specific case of Roche (a Swiss Pharma Company) showcasing its journey of wins and loses over its patents and the discussion over the emerging issues in India.
Roche and Wockhardt – Roche got its first product patent in India in 2006 (and in return, India got its first pharma product patent since its amended patent regime came into being) for Hepatitis Drug Pegasys. (Pegylated interferon alfa-2a). Its first and forthcoming patents all were being attacked by Indian Generics (not to forget various NGOs) whether through series of oppositions filed or counter-attacking to Roche’s suits of infringement. Its struggle over its patents started in 2007 when India’s first post-grant opposition was filed by Wockhardt and a Mumbai based NGO for “IN198952” on Pegasys attacking its validity claiming it to be non-inventive and not satisfying Section 3d (the section which has become the most controversial sections of Indian Patent Act since Novartis attacked its constitutionality in the famous Novartis Gleevec Case, an appeal is still pending in the Supreme Court). That was the time (and the only time) when Roche could taste success with its patent by defending it successfully. Interestingly, Assistant Controller T.V. Madhusudan (in March 2009) ruled against the recommendation of the Opposition Board to revoke the patent and held the patent to be valid. Roche successfully cleared the “enhanced efficacy” test in Section 3d of the Indian Patent Act (including the novelty and obviousness tests). Section 3d allows a novel derivative of a known compound only when such derivative shows enhancement in the known efficacy of a known compound. The efficacy is defined as therapeutic efficacy as per Madras High Court decision in Novartis Gleevec Case. Well, Interferon is a known compound and known efficacy is its antiviral and antiproliferative activity and the experimental results in the patent showed that there is indeed enhancement of therapeutic efficacy which resulted in Roche’s victory.
Roche and Cipla – After Roche’s successful stint at winning Pegasys’ patent in the opposition proceeding, it faced the first blow to its Patent Rights for Tarceva, an anti-cancer drug. Roche sued Cipla before Delhi High Court claiming that Cipla’s generic product Erlocip violates the former’s Indian Patent IN196774 claiming “Erlotinib Hydrochloride”. The trial Judge held against Roche on the ground of “public interest”, rejecting Roche’s appeal to grant an interim injunction restraining Cipla from selling a generic version of Tarceva as Cipla’s drug costs about 1/3rd of Roche’s patented drug. Roche’s subsequent appeal to Division Bench also failed miserably when not only did the bench uphold the findings of Trial Judge but also imposed costs on Roche for suppression of material patent information about Roche’s later-filed application in India (IN/PCT/2002/00507/DEL) which was specifically on Polymorph B of Erlotinib Hydrochloride (‘507 application was rejected in 2008 following the opposition filed by Cipla primarily on Section 3d. Cipla argued that Tarceva corresponds to Polymorphic Form B of active ingredient Erlotinib Hydrochloride (claimed in ‘774 patent) and that it is Form B which is more stable and suitable for solid oral dosage form than the compound disclosed in ‘774 patent comprising a mixture of Forms A and B. The interesting part was that the claims were not even construed during the trial even once. Roche’s subsequent appeal before the Supreme Court (SC) challenging the order passed by the division bench got dismissed on August 29, 2009. A key reason for the dismissal was the ongoing trial at the Delhi High Court and SC ordered the ongoing trial be expedited.
Roche and Natco – While Roche’s fight for Tarceva over Cipla’s Erlocip was still continuing at the Delhi High Court, Roche brought another suit of infringement against Natco Pharma for infringing the same Tarceva Patent (‘774 patent). The issues pertaining to:
– drug pricing and public interest (the price of Natco’s drug “Erlonat” is equally low),
– interim injunction rejection (in Roche v Cipla) as a precedent,
– Natco’s filing of Compulsory license for the same patent (Natco earlier filed for the pre-grant opposition for the same patent attacking its validity and later seeking to get compulsory license to produce a generic version of the drug and export to Nepal),
– the selection patent application ‘507 later filed in India specifically pertaining to Polymorph B and suppression of material patent information.
All these are core issues (some of them were being discussed in Cipla too) that are being argued in the ongoing trial. Natco argued and proved by showing X-ray diffraction data that Tarceva is actually Polymorph B form of the compound claimed in suit patent ‘774, and that Form B is claimed in ‘507 and not in the patent of the question thus there could be no question of infringement. The Court will be hearing the Roche v Natco matter on a daily basis from July 27, 2010, onwards.
Roche and Ranbaxy plus others Roche got another blow meanwhile (in April 2010) when it lost patent rights (IN207232) over its anti-viral drug Valcyte (Valganciclovir Hydrochloride), following the post-grant opposition filed by Ranbaxy, Cipla and four other parties including Pharma companies and Indian NGOs. Valcyte is an L-valine ester prodrug of the known anti-viral drug “Gancyclvoir”. The patent was rejected primarily on grounds of lack of inventive step over the US patent US 4957924 which claims L- valine ester prodrug of structurally similar nucleoside analog and an anti-viral drug “Acyclovir” with improved oral bioavailability and is marketed as a hydrochloride (HCl) salt of said L-valine ester as Valacyclovir Hydrochloride. It was argued that a person skilled in the art would be motivated to follow the same route to improve the oral bioavailability of Gancyclovir by forming its L-Valine ester prodrug and forming HCl salt of the said ester with a reasonable expectation of success. As regarding Section 3d here, it was held that an increase in oral bioavailability is not an increase in therapeutic efficacy as both prodrug and the original drug are the same classes of antiviral drugs and achieve the same therapeutically.
Key issues emerged
- Interpretation of the controversial Section 3d: Section 3d is under debate for quite some time now ever since the Novartis Gleevec case took off in India and its interpretation in the Madras High Court. The Court in the same case interpreted “efficacy” as “therapeutic efficacy” only and not in terms of enhancement in bioavailability or other pharmacological parameters. This ruling has been followed since then and the cases that follow and the cases we discussed above. The major issue revolving around is the lack of any qualifier for the term “efficacy” which makes the section open-ended to be interpreted by courts at their own discretion.
- There should be a detailed analysis of the claim construction in such cases. The claims were not construed in the Cipla Tarceva case. The Indian Judges seem to lack technical know-how in pharmaceutical sciences and the various complexities involved. Having more resources and training could go a long way!
- Public Interest issue: In developing countries like India, the issues like drug price and drug affordability make it unlikely that they will be able to resist pressure from their own citizens in favor of multinational drug companies like Roche. TRIPS intended to benefit both innovator and generic industries and both developed and developing nations, the balance seems to be little tilted towards the generic pharma world as pricing issue takes priority in most of the cases as discussed above
- Setback for innovation and R &D: The developed (innovator) industry should formulate some strategy for designing around drug prices in developing countries so that rewards for millions of dollars spent on research and innovation do not get diluted.
It is to be seen now when Roche’s wait for the verdict of the ongoing trials would be over and how it would affect its future business and patenting scenario in India.
About the Author: Ms. Meenakshi Khurana, a Patent Specialist in the Institute of Intellectual Property Research & Development (IIPRD) and can be reached: [email protected].