Orange Book Blog

Pfizer v. Ranbaxy, No. 07-138 (D. Del. 2007)

Pfizer sued Ranbaxy for infringement of U.S. Patent Nos. 4,681,893 and 6,455,574 after Ranbaxy filed paragraph IV certifications in its ANDA for a generic version of Caduet (atorvastatin calcium/amlodipine besylate).  The ‘893 patent claims atorvastatin calcium, which is also the active ingredient in Lipitor; the ‘574 patent claims combinations of atorvastatin sodium and amlodipine besylate.  Ranbaxy filed counterclaims seeking declaratory judgments that (1) the ‘893 patent is invalid; (2) the ‘574 patent is invalid and not infringed; and (3) a third patent, U.S. Patent No. 5,273,995, is invalid, unenforceable and not infringed.  In an opinion filed November 29, the district court granted Pfizer’s motions to dismiss Ranbaxy’s counterclaims on the ‘893 and ‘995 patents, leaving only the ‘574 patent in the case.

On August 2, 2006, the Federal Circuit affirmed the validity of the ‘893 patent in Pfizer’s case against Ranbaxy concerning Ranbaxy’s ANDA for a generic version of Lipitor.  Ranbaxy appealed to the Supreme Court, and in April, the Court denied Ranbaxy’s cert petition.  Accordingly, in the Caduet litigation, Pfizer moved to dismiss Ranbaxy’s counterclaims of invalidity of the ‘893 patent on grounds of res judicata.  In addition, Pfizer moved for partial summary judgment on the pleadings, asking for a judgment of infringement of the ‘893 patent on grounds of collateral estoppel.

In opposition to Pfizer’s motion, Ranbaxy argued that res judicata principles should be narrowly applied because the issue of obviousness was not presented at trial or adjudicated in the Lipitor litigation, and “significant factual and legal changes have occurred since the Lipitor litigation that fundamentally alter the obviousness analysis of the ‘893 patent.”  Specifically, Ranbaxy argued that the Supreme Court’s decision in KSR v. Teleflex “dramatically lowered the bar of 35 USC 103.”  The district court, however, was unconvinced, stating that Ranbaxy challenged the validity of the ‘893 patent in the Lipitor litigation, and therefore, absent fraud or a momentous legal change in constitutional rights, “Ranbaxy was required to raise all of its invalidity defenses at that time.”  Thus, the court granted Pfizer’s motion to dismiss.  In addition, because Ranbaxy did not contest infringement of the ‘893 patent, the court granted Pfizer’s motion for a judgment of infringement of the ‘893 patent on the pleadings.

In the same August 2, 2006 decision, the Federal Circuit held that Claim 6 of the ‘995 patent is invalid.  The ‘995 patent covers pharmaceutical compositions containing atorvastatin calcium.  Pfizer is currently seeking a reissue of the ‘995 patent to correct the defect in Claim 6 and to correct defects in other claims.  In the Caduet litigation, Pfizer moved to dismiss Ranbaxy’s counterclaims on the ‘995 patent on grounds that it has provided Ranbaxy a covenant not sue Ranbaxy on all remaining claims of the original ‘995 patent.

In response to this motion, Ranbaxy argued that its declaratory judgment counterclaims of unenforceability of the ‘995 patent should not be dismissed, notwithstanding Pfizer’s covenant not to sue, because “Pfizer has not agreed to provide Ranbaxy with a covenant not to sue related to any reissue of the ‘995 patent.”  Here too, however, the district court was unconvinced by Ranbaxy’s arguments.  The court stated:  “the question of whether a new patent will ever be reissued is speculative, purely hypothetical and unripe for judicial determination.  Accordingly, the Court concludes that these circumstances do not support jurisdiction under the MedImmune standard.”

As a result of the district court’s decision, Ranbaxy will not be able to launch its generic version of Caduet until at least 2010, when the ‘893 patent expires.  Pfizer will now proceed with the case, aiming to keep Ranbaxy off the market until 2018, when the ‘574 patent expires.

RELATED READING:

• FDAnews article

Warner-Lambert v. Teva Pharms. USA, No. 99-922 (D.N.J. 2007)

Warner-Lambert (part of Pfizer) and Teva have been in patent litigation over Teva’s ANDA for generic Accupril (quinapril hydrochloride) since 1999, when Warner-Lambert sued Teva for filing its ANDA with a paragraph IV certification to U.S. Patent No. 4,743,450.  According to Teva’s 2002 approval letter, Teva also filed its ANDA with a paragraph III certification to U.S. Patent No. 4,344,949, which expired on October 3, 2002, and section viii statements to U.S. Patent Nos. 5,684,016 and 5,747,504.

The ‘450 patent broadly claims pharmaceutical compositions containing an ACE inhibitor, "an alkali or alkaline earth metal carbonate to inhibit cyclization and discoloration," and "a saccharide to inhibit hydrolysis."  The ‘450 patent did not expire until February 24, 2007, with pediatric exclusivity extending until August 24, 2007.

In October 2003, the district court granted Warner-Lambert’s motion for summary judgment of infringement of claims 1, 4-10 and 12 of the ‘450 patent.  The court also granted Warner-Lambert’s motion for summary judgment of validity of the same claims.  Following a trial in May 2004, the district court ruled that claims 16 and 17 are valid, and that the ‘450 patent is not unenforceable due to inequitable conduct.  Teva appealed the findings of infringement, no invalidity for lack of enablement, and no inequitable conduct, and in August 2005, the Federal Circuit reversed the district court’s rulings on infringement and enablement and remanded the case for further proceedings.  In January 2006, the district court granted Warner-Lambert’s motion for summary judgment of infringement, leaving the issue of enablement for trial.

The district court held a trial on the question of enablement on May 2 and 3, 2007, and released an opinion last week finding the claims enabled.  The court applied the standard test:  whether the specification provides "sufficient teaching such that one skilled in the art could make and use the full scope of the invention without undue experimentation."  Teva argued that the claims of the ‘450 patent are extremely broad and the specification provides insufficient guidance to develop the full range of pharmaceutical formulations encompassed by the claims.  In addition, Teva argued that numerous failures to arrive at operative embodiments of the claims proved nonenablement.  The court, however, found the testimony of Warner-Lambert’s expert witness (who "wrote the book on stability of pharmaceutical formulations") to be more persuasive than the testimony of Teva’s expert.  The court was convinced by Warner-Lambert’s expert that one skilled in the art could readily practice the full scope of the claimed invention through routine experimentation.  In addition, the court found that none of the purported "failures" proffered by Teva were evidence of lack of enablement.

Last week’s court decision could impact other cases in which the ‘450 patent has been asserted.  For instance, Warner-Lambert filed suit against Teva and Ranbaxy in January 2005, after Teva announced that it began shipping generic quinapril HCl tablets in partnership with Ranbaxy.  In addition, Schwarz Pharma AG, an exclusive licensee of the ‘450 patent, has asserted the patent against in litigation concerning generic versions of Univasc (moexipril).

The Lovenox patent infringement litigation between Aventis and Teva/Amphastar is making its second trip to the Federal Circuit.  In February, following remand from the Federal Circuit last year, a federal district court in California held that the Lovenox patent is unenforceable due to inequitable conduct.  The appeal may emerge as a litmus test of how far the CAFC is willing to go in lowering the bar on inequitable conduct, especially in terms of what it takes to prove deceptive intent.  In general, the party asserting inequitable conduct must prove each prong of inequitable conduct (i.e., materiality and deceptive intent) by clear and convincing evidence.

In recent cases, the CAFC has expanded the scope of what counts as a material omission, including the omission of information that would have had no bearing on patentability.  Thus, a practitioner may even comply with Rule 56 (37 CFR 1.56), and still be found to have withheld material information.  This bar-lowering has occurred primarily via the emergence of the “reasonable examiner” standard.  Hence, materiality is judged not by the PTO’s rules, but by a post hoc litigation-induced evaluation of what information a hypothetical “reasonable examiner” would (or should) have wanted during the ex parte prosecution of the patent application.

Moreover, defendants may no longer need to prove deceptive intent by clear and convincing evidence.  Instead, a “guilt by omission” standard seems to have emerged.  If the omitted information is “highly material” and if the patentee cannot proffer a reasonable explanation for the omission, then a court is permitted to infer deceptive intent.  (Of course, the line between ordinary materiality and “high materiality” is a bit fuzzy, especially if an omission can be highly material even when it would have had no effect on patentability.)

In the Lovenox district court case, the district court went one step further:  The court appeared to have shifted the burden to Aventis to disprove deceptive intent (e.g., after finding that Teva/Amphastar had made out a prima facie case of deceptive intent).  It will be interesting to see where the CAFC goes with this one.

The parties appear reluctant to tread into the legal issues surrounding the CAFC’s recent inequitable conduct jurisprudence.  After all, a sizeable portion of the judges have not yet bought into the recent trend of making it easier to prove inequitable conduct.  Instead, the parties have elected to focus on several alleged clear errors in the district court’s fact-finding.  Perhaps that’s the best approach, anyway.  By their very nature, inquires into an individual’s intent must be fact-intensive. 

Of course, the CAFC may do well to pay more heed to the post-1978 developments in antitrust law, where scholars of all stripes have generally rejected the value of intent-based evidence.  Inequitable conduct arose in 1945 and came of age during that era of legal moralism that emerged from antitrust cases like Standard Oil.  Antitrust law has now largely unburdened itself of Standard Oil and its progeny.  To the degree that inequitable conduct is a relic of that bygone age, why must we retain it in patent law?

Meanwhile, the FDA has still not yet approved any generic versions of Lovenox (enoxaparin sodium).  Lovenox consists of a complex mixture of oligosaccharides that has been shown to have improved anticoagulant effects over other low-molecular-weight heparins (LMWHs).

Earlier this month, Momenta Pharmaceuticals announced that the FDA rejected its ANDA for M-enoxaparin, apparently based on concerns about the generic drug’s immunogenicity.  In other words, the FDA was concerned that it may provoke an unwanted immune response in humans.  Moreover, according to Momenta's press release, "the FDA clarified that all applications for enoxaparin products must address the potential for immunogenicity of the drug product."

Momenta is working with Swiss generic manufacturer Sandoz to develop its generic product.  The news of the rejection caused Momenta’s stock to lose nearly 60% of its value in a single day.  In the intervening weeks, Momenta’s stock value has continued to tumble another 4-5%.

APPEAL BRIEFS:

• Aventis opening brief
• Amphastar opposition brief
• Teva opposition brief
• Aventis reply brief
• Sandoz amicus brief

RELATED READING ON FDA ACTION:

• Bloomberg article
• Pharmalot post
• WSJ Health Blog post