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Mylan Wins One, Loses One

In Pfizer v. Mylan Labs (02cv1628) a patent infringement action was brought by Pfizer under U.S. Pat. Nos. 4,572,909 [1] and 4,879,303 [2], which cover an amlodipine besylate product sold under the trade name Norvasc®.

Mylan filed an Abbreviated New Drug Application (“ANDA”) for approval to sell generic amlodipine besylate. Mylan certified pursuant to 21 C.F.R. 314.94(a)(12)(i)(A)(4) (paragraph IV certification [3]) that it was seeking approval to market its generic copy of Norvasc® prior to the expiration of the ’909 and ’303 patents. The application stated that to the best of Mylan’s knowledge neither the ’909 nor the ’303 patents would be infringed by the manufacture, use or sale of the proposed generic amlodipine besylate.

Pfizer sued Mylan for infringement of both patents and sought “[a]n order preliminarily enjoining and permanently enjoining [Mylan] from making, using, selling, offering to sell, or importing into the United States the Mylan Amlodipine Tablets described in ANDA No. 76-418 until after the expiration of the ‘909 patent term, . . ., and after the expiration of the ‘303 patent term . . .”

Mylan argued that Pfizer’s claims for inducing infringement and infringement of the ‘909 patent should be dismissed for lack of subject matter jurisdiction. According to Mylan, since the ‘909 patent expired on July 31, 2006, there is no longer a case or controversy with respect to the ‘909 patent. Pfizer responded that the district court retains jurisdiction over a patent infringement case when the patent has expired but the period of pediatric exclusivity remains at issue. Because the ‘909 patent expired on July 31, 2006, the court found that the rights secured by the patent are no longer protectable and entitlement to injunctive relief becomes moot because such relief is no longer available.

Pfizer had sought to continue to include the ‘909 patent in the litigation in an attempt to reinstate pediatric exclusivity as to Mylan. The FDA has confirmed that Mylan was the first generic company to file on all strengths of Norvasc(R) Tablets and is therefore eligible for 180 days of market exclusivity. The FDA has indicated that the exclusivity will begin to run from the earlier of the commercial launch of the Mylan product or a final court decision concerning the pending litigation between Pfizer and Mylan.

In Ortho-McNeil Pharmaceutical v. Mylan Laboratories (04-cv-01689), Ortho (a subsidiary of Johnson & Johnson) claimed that its U.S. Pat. No. 4,513,006 [4] was infringed by Mylan. The claims of the ’006 patent cover the drug topiramate, pharmaceutical compositions containing topiramate, and a method of using topiramate to treat convulsions. Ortho holds an approved New Drug Application (“NDA [5]”), under Section 505(a) of the Federal Food Drug and Cosmetic Act (“FFDCA [6]”), 21 U.S.C. § 335(a), for topiramate tablets and topiramate capsules, which are marketed in the United States as the anticonvulsant Topomax®.

In 2001, Mylan filed an Abbreviated New Drug Application (“ANDA”), pursuant to Section 505(j) of the FFDCA, to market topiramate before the expiration of the ’006 patent claiming that the ’006 patent is invalid. Ortho then filed a motion for a preliminary injunction to enjoin Mylan from marketing or selling topiramate.

To get a preliminary injunction, a plaintiff must show: (1) a reasonable likelihood of success on the merits of its claims; (2) irreparable harm if an injunction is not granted; (3) a balance of hardships tipping in its favor; and (4) the injunction’s favorable impact on the public interest. In order to demonstrate a likelihood of success on the merits on a particular claim of patent infringement, Plaintiffs must show that (1) Defendants likely infringe the patent, and (2) the claims of the patent will likely withstand Defendants’ challenges to validity. The court found that Ortho has demonstrated a likelihood of success in establishing that Mylan would infringe the ’006 patent and that the infringed claims of the ’006 patent will likely withstand Defendants’ challenges to validity.

In arguing that claim 1 of the ’006 patent (the only independent claim) is invalid as obvious, Mylan relies entirely on the expert opinion of Dr. Laurens Anderson. The court held that:

The approach espoused in Anderson 1 has significant problems that lead this Court to conclude that, in relying on it, Mylan has not raised a substantial question of obviousness. To begin with, as Ortho contends, Dr. Anderson has merely followed the path of development that Dr. Maryanoff claims to have followed. (See New Product Conception Record, Harth Conf. Decl. Ex. Q.) Dr. Anderson begins with the problem he believes Dr. Mayanoff was attempting to solve, follows the path he believes Dr. Maryanoff took, and ends up with topiramate. This is a hindsight-based obviousness analysis. The Federal Circuit has made clear that the inventor’s chosen path is irrelevant: “[T]he path that leads an inventor to the invention is expressly made irrelevant to patentability by statute. . . [T]his inquiry, as a matter of law, is independent of the motivations that led the inventors to the claimed invention.” Life Techs., Inc. v. Clontech Lab., Inc., 224 F.3d 1320, 1325 (Fed. Cir. 2000). Rather, § 103 requires that the obviousness inquiry must be performed from the perspective of one of ordinary skill in the art. 35 U.S.C. § 103(a).

Furthermore, applying the “motivation-suggestion-teaching” test, this Court finds significant gaps in the path Dr. Anderson follows: 1) Dr. Anderson implies that knowledge of Thomas “inspired” the idea of substituting a sulfamate group for a phosphate group. (Anderson 1 at 12.) This leaves unexplained, however, how knowledge that replacing a part of 5′-AMP with a sulfamate group produces an antibiotic would motivate the idea of sulfamoylation of a fructose derivative to produce a FBPase inhibitor. Furthermore, Dr. Danishefsky contends that the research on 5′-AMP and nucleocidin should not be considered to be part of the analogous prior art. (Danishefsky Decl. 19.) Even if it were shown to be relevant prior art, Dr. Anderson does not explain how knowledge of modifications to produce antibiotic potency would motivate modifications to produce gluconeogenic enzyme inhibition. 2) Dr. Anderson states that Dr. Maryanoff selected the “well-known” 2,3:4,5-di-isopropylidene fructose (“DPF”). (Anderson 1 at 17.) Dr. Anderson gives no explanation of what would have suggested DPF to one of ordinary skill in the art. Dr. Anderson states that Dr. Maryanoff “suggested that the desired inhibitory properties might be present in fructose derivatives . . .” (Id. at 12.) Dr. Anderson’s statement that it was Dr. Maryanoff himself, and not something in the prior art, that suggested researching fructose derivatives for enzyme inhibitors raises the inference that Dr. Anderson’s ideas in this regard may have been original and inventive. Certainly, Dr. Anderson has not pointed to anything that would have suggested the use of fructose derivatives to Dr. Maryanoff. This is a crucial gap in the theory, since Dr. Anderson proposes that by choosing a particular fructose derivative (DPF), and then choosing to sulfamoylate it, one ends up with topiramate. There is no basis to infer that one of ordinary skill in the art would have been motivated to select DPF to sulfamoylate.

Ortho argued that the claimed invention would not have been obvious based on four categories of objective evidence of non-obviousness: (1) Unexpected results; (2) Commercial success – Topamax® is the top-selling branded neurology product in the US.; (3) Copying – FDA has received nine ANDA applications for topiramate formulations; and (4) Industry recognition.

Overall, the Court found that all four factors in the preliminary injunction analysis weigh in favor of granting Ortho’s motion for a preliminary injunction.