More Problems for Tarceva

Revolutionary anticancer drug Tarceva seems to be moving more into problems now. Last month, the Delhi High Court in highly unexpected findings that may create setback for drug research companies in India concluded that if an active ingredient (Erlotinib hydrochloride) of the drug (Tarceva) is sold in a polymorphic Form then that active ingredient in not covered/protected by the compound (drug substance) patent. To cut short, Pfizer received Indian Patent No. 196774 (the ‘774 patent) for Erlotinib hydrochloride (corresponding of US 5,747,498) and had a pending application for polymorphic Form B of Erlotinib hydrochloride (corresponding of US 6,900,221) which eventually got rejected in pre-grant opposition filed by Cipla. Both corresponding US patents are listed with Orange Book as Tarceva marketed tablet formulation contain polymorphic Form B. Roche brought infringement suit against Cipla with respect to granted patent in India (the ‘774 patent) but in counter-claim Cipla argued (rather framed argument) that Tarceva sold in India is polymorphic Form B of Erlotinib hydrochloride and not Erlotinib hydrochloride per se covered by granted the ‘774 patent. The Court unhesitantly agreed with Cipla’s arguments that Tarceva sold in India is not covered by granted ‘774 patent claiming Erlotinib hydrochloride but is a polymorphic Form B for which Roche do not hold a patent. Knowing that the Indian Courts are unfamiliar with even basic understanding of pharmaceutical patents and technical know-how of pharmaceutical science, Cipla opportunistically deceived the divisional bench by arguing that the ‘774 patent covering Erlotinib hydrochloride per se is a mere admixture of polymorph A and B of Erlotinib hydrochloride. Cipla further argued that since the ‘774 patent is admixture of polymorph A and B of Erlotinib hydrochloride and marketed Tarceva tablet is polymorphic Form B, Roche cannot sue them for the ‘774 patent. Further capitalizing on admixture of polymorph A and B story, Cipla also challenged the validity of the ‘774 patent arguing that polymorph are not patentable under section 3(d). Unfortunately, the divisional bench was so inclined by Cipla’s arguments that the Court penalized Roche to pay Cipla Rs. 5 Lakhs (approx. USD 10000) for making false case against Cipla for the drug Tarceva for which Roche did not yet hold a patent. Surprisingly, the divisional bench never even bothered to look into independent claim of the ‘774 patent which reads as –

“A novel [6,7-bis(2-methoxyethoxy)quinazolin-4-yl]-(3-ethynylphenyl) amine hydrochloride compound of the formula A.”

Clearly the independent claim is no where restricted to any polymorph form or admixture polymorph A and B of Erlotinib hydrochloride (as argued by Cipla). The independent claim is covering compound Erlotinib hydrochloride per se and technically such claim cannot be circumvented and designed around by any polymorphic Form of Erlotinib hydrochloride (even a fresher working in pharmaceutical patents reasonably knows that). Why the divisional bench do not refer to the claims of the ‘774 patent? Though after reading the case we feel even the divisional bench would have referred the claims of the ‘774 patent they would not have understood anything (we are least confident about the divisional bench familiarity with basic pharmaceutical science and claim construction). But what is really interesting is the tactic used by Cipla’s lawyers (though completely and technically fallacious) that worked in favor of Cipla. What Roche lawyers can do in a case where unexpected arguments were raised by Cipla’s lawyers (which they possibly never thought in wildest dream) and the divisional bench was not familiar with nuances of basic pharmaceutical science and patent? Just imagining what Roche counsels back in Swiss Headquarters thinking about the judgment?

At least this case gives a cautionary picture that patentees should not be surprised to hear any unexpected reasoning from the judiciary and may think twice before spending money in procuring patents in India that may worth nothing after issuance. At least such decisions will be enough to shatter confidence of small companies and inventors who spent a decent amount of money to file and procure patents in India. How such small companies and inventors will be able to enforce their patents (most of them even do not have enough money to fight litigations). Companies like Cipla will always take advantage of system shortcomings, sometimes playing trump card of public health for their business interests whereas research/innovation will continue to die the way it is dying in India for so many years, decades.

Coming back to Tarceva, lately the United States Food and Drug Administration (FDA) announced a black box warning for Tarceva (read here). In a letter dated April 2009, Genentech and OSI said that there had been reports of patients suffering gastrointestinal perforations while undergoing Tarceva therapy. This risk is greatest for patients receiving concomitant anti-angiogenic agents, corticosteroids, NSAIDs, and/or taxane-based chemotherapy, or who have prior history of peptic ulceration or diverticular disease. According to the letter, some instances of perforation had been fatal. The letter also said that some Tarceva patients had developed bullous, blistering and exfoliative skin conditions, which in some cases were suggestive of Stevens-Johnson syndrome or toxic epidermal necrolysis. Finally, the letter warned that patients treated with Tarceva had experienced corneal perforation or ulceration. Other eye disorders including abnormal eyelash growth, keratoconjunctivitis sicca and keratitis, have also been observed with Tarceva treatment. Last year in October, we reported Tarceva post-approval study reported a death. Such studies and report are often done by Innovator to avoid any post-launch tragedy.