Sunday, June 29, 2008

Lipitor Settlement: What Lies Beneath? Part II

Strategically Lipitor settlement seems to be more favorable for Ranbaxy as this provides certainty for Ranbaxy to launch generic product in the United States without any patent hurdle and may allow recouping the expenses made in Lipitor litigation worldwide but what benefits Pfizer from settlement? Pfizer too avoided legal cost that would be spend further in litigation and importantly put an end to nightmarish litigation which witnessed the ‘995 patent going down.

What about 180-day market exclusivity?

Technically the 180-day market exclusivity will trigger soon after the expiration (March 2010) of the genus patent but Ranbaxy, under the terms of the agreement, would delay the launch until November 2011 which would possibly lead to forfeiture of Ranbaxy’s right to 180-day market exclusivity. 21 USC 355 (j)(5)(D) states that if the first applicant fails to market the generic product within 75 days from the date of FDA final approval of ANDA that will lead to forfeiture of 180-day exclusivity period. And in case of forfeiture, any later ANDA applicant may market its generic product upon receiving FDA final approval. Interestingly, if Ranbaxy forfeits its 180-day market exclusivity then the Lipitor generic space will open much earlier than the expected (that is before July 2010). However, it would still not be easy for any generic player to cross hurdles of Pfizer’s polymorphs and amorphous patents and step into Lipitor generic fortune. Pfizer not only litigated its patents strategically but possibly put an end to prized 180-day market exclusivity.

Lipitor Settlement: What Lies Beneath?

Historical patent litigation between world’s largest drug manufacturer Pfizer and world’s most aggressive generic company Ranbaxy over biggest ever blockbuster drug Lipitor has finally ended in unexpected climax with both Pfizer and Ranbaxy settling all their patent litigations worldwide. Under the agreement, Pfizer voluntarily licensed Ranbaxy to sell generic versions of Lipitor in the United States effective November 30, 2011. In addition, the agreement provides a license for Ranbaxy to sell generic versions of Lipitor on varying dates in seven additional countries: Canada, Belgium, Netherlands, Germany, Sweden, Italy and Australia. Thought the settlement is win-win for Ranbaxy and Pfizer but gives more strategic value to Ranbaxy. It would be really interesting to revisit and trace some of the facts and carefully look what lies beneath the historical settlement?

Pfizer’s Strategy was Ranbaxy’s Dilemma

It all triggered when Ranbaxy filed an abbreviated new drug application (ANDA) with the United States Food and Drug Administration seeking marketing approval for generic equivalent of Lipitor before the expiration of Orange Book listed patents. Pfizer sued Ranbaxy within statutory timelines (45 days) and filed civil action for alleged infringement in the District Court. During the course of litigation proceedings, Ranbaxy strongly challenged the validity of the US 5,273,995 patent and also questioned patent term extension awarded to the US 4,681,893 (genus patent). Alas Ranbaxy failed to convince the District Judge any of its arguments and lost to Pfizer. Ranbaxy appealed and this time CAFC partially reversed the district court judgment, invalidating the ‘995 patent. CAFC ruling gave Ranbaxy the grandest legal victory by any generic company in the United States and importantly entitlement to 180-days market exclusivity. This mean that Ranbaxy’s precious 180-days market exclusivity will be triggered soon after the expiration of the genus patent. Though most of the business and news analysts predicted that Ranbaxy will be able to bring generic equivalent soon after expiry of the genus patent but it was not that easy for Ranbaxy to breakthrough ‘Lipitor generic space’ even after knocking down the ‘995 patent. Till here, Pfizer strategically avoided Ranbaxy from suing for other orange book and non-orange book listed patents covering different polymorph and amorphous forms. Probably Pfizer (legal team) thought waiting till Ranbaxy launches its generic equivalent and then sue for infringement of polymorph and amorphous patents. This strategy not only would hinder Ranbaxy’s generic equivalent but also may give Pfizer an opportunity to claim treble damages against the willful infringement. Though Patent Circle is not sure whether Ranbaxy used different form other then patented by Pfizer and planned declaratory judgment for non-infringement prior to launch of its generic equivalent or was planning to challenge the validity of Pfizer’s patents for polymorph and amorphous form but what is sure that Pfizer would have hunted down Ranbaxy for polymorph and amorphous patents.

Patent Circle believes that Pfizer strategically litigated Lipitor against Ranbaxy and kept polymorph and amorphous patents out of Para IV litigation so that Pfizer may unfold them in separate litigations. Pfizer not only used patents against Ranbaxy but also in parallel strategically filed a citizen petition with the United States FDA regarding amorphous atorvastatin. In its petition, Pfizer concerned about higher levels of impurities and inferior stability of other polymorphs and amorphous forms that may be used by generic companies. Pfizer also stated that the pending application for a generic version is in an amorphous form (though not mentioned the name of company but was possibly referring to Ranbaxy ANDA). In March 2008, Pfizer extended its strategy by filing fresh infringement suit against Ranbaxy for infringement of two non-orange book listed patents – US 6,087,511 and US 6,274,740 both covering processes for the preparation of amorphous Atorvastatin which suggest that Ranbaxy possibly used amorphous atorvastatin calcium for their proposed ANDA. The process patents are due to expire in July 2016 and would mean that if Pfizer succeeds in wining the litigation that would delay Ranbaxy’s generic product till 2016. This litigation put Ranbaxy in dilemma whether to launch generic soon after the expiration of genus patent with a possible risk of treble damages or wait till litigation get over but that may possibly risk of running out 180-days market exclusivity without even launching the generic product for which Ranbaxy played such a risky game. Pfizer’s Strategy was Ranbaxy’s Dilemma.

To be continued …

Friday, June 27, 2008

Cipla Patents Salt and Complex of Blockbuster Drug Substances in India

Mumbai-based Cipla has lately obtained patents for new form of two blockbuster drug substances, namely, esomeprazole and alendronate. In past, Cipla has constantly accused foreign MNCs for ever-greening of patent monopoly and strongly opposed patenting of so-called trivial improvements but in general practicing the same in India. In April 2008, Mumbai Patent Office issued Patent no. 219034 to Cipla for inclusion complex of esomeprazole with cyclodextrins which technically should fall under section 3(d) of the Patents Act, 1970 (that is complexes of known substances). Surprisingly the search report (ISR) of equivalent WO02098423 cited one ‘X’ category reference and eleven ‘Y’ category references against the novelty and non-obviousness of the invention but still Cipla managed to get patent in India. Though Patent Circle went through the WO equivalent but couldn’t find any data suggesting and relating to enhanced or improved efficacy. Also in April 2008, Mumbai Patent Office issued Patent no. 219022 for alendronate monosodium salt which also falls under section 3(d) (that is salt of known substances). In this case also the search report (ISR) of equivalent WO03033508 cited five ‘Y’ category references against the non-obviousness of the invention. Patent Circle also scanned the disclosure of WO equivalent but yet again couldn’t find any data suggesting and relating to enhanced or improved efficacy. Surely it would be really interesting to know on what basis Cipla managed to overcome the efficacy barriers under section 3(d). Unfortunately, Indian Patent Office (IPO) has ill-practice of issuing patent in India if patent for same invention is granted in other country particularly Europe and US and that also without giving any considerable thought. Possibly Cipla too provided copy of granted European/US patent to have patents issued by the Mumbai Patent Office.

Often public health interest organizations criticized patenting of polymorphs or other forms of known substances (considering such improvements as trivial modifications) and keep targeting foreign MNCs of being patent freaks but why avoided same practice against the Indian companies. The only reason they may give that the foreign MNCs will charge excessive price for patented drugs whereas domestic companies will not. Interestingly last year Cipla received Government notice demanding Rs. 24.23 crore for alleged overcharging on antibiotic ciprofloxacin during the period April 2006 to March 2007. Earlier Cipla also received similar notices from the National Pharmaceutical Pricing Authority (NPPA) demanding as estimated Rs. 941.92 crore for alleged overcharging till March 2006 for five drugs, namely, Salbutamol, Theophylline, Ciprofloxacin, Norfloxacin and Cefadroxil. Just note this overcharging is for generic drugs what if Cipla start marketing and pricing patented drugs. Anyhow bottom line of any business is profit (not public health) and it seems difficult to predict whether NGOs are more confidants to Indian generic companies or to public.