Endo Pharmas. Inc. v. Mylan Pharmas. Inc.

After claim construction resulted in stipulation of infringement, asserted claims were not invalid as anticipated, obvious or failing to meet the written-description and enablement requirements.

Spring 2014

GENERICally Speaking

Case Name: Endo Pharmas. Inc. v. Mylan Pharmas. Inc., Civ. No. 11-00717 (RMB/KW), 2014 U.S. Dist. LEXIS 10037 (D. Del. Jan. 28, 2014) (Bumb, J.)

Drug Product and Patent(s)-in-Suit: Frova® (frovatriptan succinate); U.S. Patents Nos. 5,464,864 (“the ’864 patent”), 5,637,611 (“the ’611 patent”), and 5,827,871 (“the ’871 patent”)

Nature of the Case and Issue(s) Presented: Although disputing the court’s claim construction, Mylan conceded prior to trial that it infringes or will infringe the asserted claims. But Mylan maintained that the patents-in-suit were invalid under the doctrines of anticipation, obviousness, written description, and enablement. After considering the evidence and the parties’ post-trial submissions, the court found that: (i) Endo had waived and was thus judicially estopped from pursuing claims against Mylan related to the ’871 and ’611 patents in this litigation; and (ii) the asserted claims of the ’864 patent were valid.

Why Endo Prevailed:  The following context is necessary for understanding the court’s decision. Frovatriptan monosuccinate monohydrate is a hydrated salt form of frovatriptan, which means that it is a crystalline form of a compound in which water is part of the crystal lattice. There are two enantiomers for frovatriptan. The specific frovatriptan enantiomer used as the API in Frova is the (R)-(+) enantiomer.

On August 7, 2013, the court construed the disputed claim terms. After noting that the parties agreed that the compound includes “all R [enantiomers] and no S to all S and no R, and every ratio in between,” the Court determined that the term “compound of (general) formula (I)” refers to “the formula without regard to its stereochemistry.” Second, the court construed the term “or a salt, solvate or hydrate thereof,” to mean “or one or more of salt, solvate or hydrate thereof.” Thirdly, the court construed the term “treatment of a condition wherein a 5-HT1-like agonist is indicated,” to mean “treatment without prophylaxis.”

The court firstly addressed whether Endo abandoned its claims related to the ’871 and ’611 patents. The court ruled that it had. The court found that Endo’s abandonment of those claims occurred in the midst of trial after some evidence relating to those patents already had been presented. Endo stated that “with this [terminal] disclaimer everything rises and falls on the ’864 patent, we can litigate the ’864 patent and that will govern what occurs in the case.” Hence, it was the court’s view that any further effort to pursue claims against Mylan related to the ’871 and ’611 patents in this litigation would be judicially estopped. The court based its decision not on the terminal disclaimer, but on the unequivocal statements of counsel signifying Endo’s intent to abandon its claims.

Next, the court addressed whether the ’864 patent was invalid. Mylan argued that U.S. Patent No. 4,257,952 (“Mooradian ’952”) anticipated the asserted claims in the ’864 patent. Mooradian ’952 is a prior-art patent that was considered by the USPTO in the prosecution of the ’864 patent. It is undisputed that claim 1 of Mooradian ’952 “encompasses frovatriptan” and “the elements of frovatriptan.” The issue, then, is whether the particular genus disclosed in claim 1 of Mooradian ’952 is so defined and limited that a POSA can at once envisage each species. The court adopted Endo’s expert’s opinion that although a POSA could tease out the elements of frovatriptan from the broad disclosure in Mooradian ’952, s-he would not immediately envision the frovatriptan molecular structure. Mooradian ’952 lists four “preferred” groups of compounds which provide limitations on the substituents in certain positions on the compounds. Although these preferred groups narrow the broader genus of disclosed compounds in Mooradian ’952, they still encompass “hundreds or thousands of compounds,” and none those preferred groups include the frovatriptan structure.

Next, Mylan argued that the asserted claims of the ’864 patent are: (i) obvious in light of prior-art references Mooradian ’952 and/or Mooradian 1977,  a journal article by the same author. The court found that, individually and separately, the Mooradian references teach a preference for a 3-dimethylamino substituent, which is not found within frovatriptan, and do not suggest a preference for a 6-carboxamido. They further do not suggest utility in treatment of a condition wherein a 5-HT1-like agonist is indicated (claim 2) or migraine (claim 3). And, of particular importance to the court, both references were disclosed to and considered by the USPTO during prosecution of the ’864 patent, and yet the USPTO issued the ’864 patent notwithstanding these prior art references.

Mylan’s second obviousness argument was premised on the fact that several prior-art publications taught the choice of 5-CT as the lead compound and that a POSA starting with 5-CT would have found it obvious to conformationally constrain 5-CT to form the tetrahydrocarbazole in a single step, followed by routine methylation to obtain frovatriptan. However, the court found that while the discovery of 5-CT may have initially represented an advance in the field of migraine, the subsequent development of sumatriptan reflected a significant shift in the field such that a POSA desiring to create a 5-HT1-like agonist or anti-migraine compound would have chosen sumatriptan as the lead compound. Mylan’s argument that 5-CT would be chosen as the lead compound “prioritizes potency to the exclusion of any other desired characteristics and fails to account for any unwanted side effects.” Hence, as of the priority date sumatriptan, not frovatriptan, had demonstrated qualities a POSA would look for in a potential migraine candidate—efficacy, tolerability, and minimal side effects in humans.

Finally, Mylan argued that the ’864 patent fails to describe and enable: (i) the separation of the enantiomers of frovatriptan; or (ii) the treatment of migraine that is expected to present. The court again disagreed. Mylan contended that because the claims were broadly construed, the ’864 patent must specifically describe and enable the separation of the enantiomers of 3-methylamino-6-carboxamido-1,2,3,4-tetrahydrocarbazole. But because the court’s construction did not include any stereochemical limitations, the disclosure is not insufficient due to failure to describe how to obtain the particular (R)-(+) frovatriptan form of the compound. The court held that a POSA would understand the chemical compound to describe the compound as a racemic mixture or as each enantiomer. That—in combination with the resolution techniques well-known to a POSA—renders the disclosures in the ’864 patent application sufficient to reasonably convey to those of skill in the art the subject matter of the claimed invention and that the inventors were in possession of it. In response to Mylan’s argument that the ’864 patent is silent as to the treatment of migraine that is “expected to present,” the court found that a migraine is “expected to present” when a migraine sufferer experiences any symptoms that are understood to typically accompany migraine. In other words, the court drew the line separating “treatment” and “prophylaxis” at the point when migraine symptoms begin to manifest. Moreover, the ’864 patent describes a week-long treatment regimen that includes dosing information, dosage amount, how many times a day to administer that dosage amount, and for how long the treatment may be continued. Therefore the asserted claims are adequately described and enabled.

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