“Indian drug manufacturer Ranbaxy is contesting US multinational Pfizer in 17 countries. It is filing for the right to manufacture generic versions of the world’s bestselling drug Lipitor and a combination drug Caduet, in the us. At the crux of the dispute is Pfizer’s designs on a patent extension by combining Lipitor with another drug: Norvasc.
Ranbaxy senses a weakness in Pfizer’s case and is questioning the US multinational’s rights in several countries. It has also filed applications to market, and make generic versions of Caduet. Pfizer is contesting these applications. Shamnad Basheer of George Washington University Law School, however, believes that the Caduet patent will be invalidated since it does not really represent any “inventiveness”.
“The litigation can have a bearing on the Novartis dispute in India on the generic blood cancer drug, Gleevec,” he said. Basheer believes that Caduet will not be patentable if it’s a sum of the properties of Lipitor and Norvasc. “But Lipitor’s patent has to end for a generic to come out,” he notes.
For those of you interested in the “technical” intricacies of the dispute, these were my interview answers to Rohan George:
Q. Could you comment generally on the tenability of Ranbaxy and Pfizer’s legal position on the Caduet dispute?
Ans. This is a combination patent. Caduet combines the active ingredients in two of Pfizer’s top-selling drugs — its cholesterol drug Lipitor (atorvastatin calcium) and its hypertension drug Norvasc (amlodipine besylate). It won FDA approval in 2004.
As to whether such a combination is patentable would depend significantly on whether it was “obvious” to combine the two drugs.
The recent Norvasc invalidation by the CAFC suggests the application of the non obviousness standard in a more rigorous way and it is likely that the combination of Amlodipine and Lipitor will be held “obvious” one and therefore invalid.
I think Pfizer is right that a challenge to patent no ‘893 alone will not stand. This is the patent covering Lipitor and this had been held as “valid” by the CAFC. Res Judicata principles may therefore estop Ranbaxy from challenging the individual validity of this patent. The amlodipine besylate patent (Norvasc) has been invalidated and Ranbaxy can certainly rely on this. Interestingly enough, Pfizer does not rely on this patent (‘303) in the Caduet complaint—even though the complaint was filed prior to the invalidation of Norvasc by the CAFC. However, even assuming that both Lipitor and Norvasc patents are invalid, a drug combining these two obvious susbtances could in theory, still be patentable, if the “combination” is inventive or not obvious. However, as I have stated earlier, this combination is not likely to pass muster as a “non obvious” or “inventive” combination. The combination patent number is ‘574.
2. At what point did this dispute start?
As you are well aware, under US law, the filing of a Para IV certification along with an ANDA by a generic is treated (through an artificial construct) as a “patent infringement”. And this filing by Ranbaxy of Para IV triggered off the law suit by Pfizer.
3. Reports have come in that the patent for Norvasc has been invalidated by the US Court of Appeals for the Federal Circuit. Is Pfizer’s patent on Caduet valid any longer? Is Caduet not merely a combination of two pre-existing drugs?
I’ve already answered this in answer 1 above.
4. If the patent on atorvastatin is set to expire in 2010, and the patent for Caduet expires in 2018, how can Ranbaxy contest Pfizer’s claim of patent infringement?
As I’d already mentioned the crux of this dispute will be on the validity of the ‘574 patent: which is a combination patent. The atorvostatin patent (‘893) cannot be challenged, since it has already been held as “valid” by the Federal Court in the Lipitor litigation—and therefore under principles of res judicata, ranbaxy is estopped from bringing this issue up again.
5. What impact will the final outcome of the case have on the consumer and public health in the US and internationally?
Given the recent trend of the CAFC to apply the non obviousness standard more stringently, I think the combination patent (‘574) will be invalidated. This is more so, since it appears that this combination was designed for the sole purpose of extending patent life, and does not really represent any kind of “inventiveness”.
This litigation will have tremendous implications for section 3(d) and the Novartis dispute. Section 3(d) states that “combinations” shall be considered to be the same as the earlier known substance, unless it differs significantly in properties with regard to efficacy. Further, section 3(e) states that a substance obtained by mere admixture resulting only in the aggregation of properties of the components thereof is not patentable. Thus, if Caduet represents a mere sum total of the properties of Lipitor and Norvasc and nothing more, then it is not patentable. If the patentable is invalidated, consumers would therefore benefit from cheaper generic versions, as the monopoly on Caduet will come to an end now (and not last till 2020). However, for a generic to bring out a version, the Lipitor patent has to end. Without the Lipitor patent coming to an end, any generic selling the combination will have infringed the Lipitor patent.
However, if the combination patent is not invalidated, the interesting question to ask would be: does the consumer really need access to this combination drug? Can a consumer not buy a cheaper version of generic Lipitor and generic Norvasc separately and have them together? How useful is the “combination” itself for the consumer? It also needs to be noted that this analysis may in part, inform a court (albeit indirectly), when it decides the issue of “non obviousness” re: the ‘574 patent.
6. Ranbaxy had apparently earlier fought and lost a lawsuit in the US in order to invalidate a patent on Lipitor. Will that affect the litigation in the US? In what manner? Pfizer is quoted as saying that Ranbaxy is barred “from attacking the validity or enforceability of the patent term extension” and “the infringement, validity and enforceability” of the patent itself.