Sumitomo Dainippon Pharma Co. Ltd. v. Emcure Pharmaceuticals Ltd. (Fed. Cir. Apr. 16, 2018)
Abstract
This case is about claim construction, i.e., the scope of a claim reciting the structural formula of an active ingredient in antipsychotic drug LATUDA® or lurasidone hydrochloride. Central to Hatch Waxman litigation, the issue was whether the claim covered narrowly only a racemic mixture of the active ingredient, or more broadly any of its enantiomers as well as mixtures thereof. The CAFC decided that the claim covered at least the specific enantiomer found in defendant’s generic version of the drug product, i.e., the (-) enantiomer as depicted in the claimed formula.
Invention
The only claim under review was claim 14:
14. The imide compound of the formula:
or an acid addition salt thereof.
Background and Posture
U.S. Patent 5,532,372, titled, “Imide derivatives, and their production and use,” issued Jul. 2, 1996 from an application filed on Aug. 30, 1993 as a continuation of an application filed on Jul. 5, 1991 (abandoned), claiming priority to a JP application filed Jul. 6, 1990.
The antipsychotic (bipolar disorder) drug lurasidone was FDA approved Dec. 7, 2011. The patent term was extended up to July 2, 2018 (full 5 yrs.). An ANDA with Paragraph (IV) certification was filed by Emcure and Notice was served on Sunovion (FDA approval holder) in December 2014. Sumitomo/Sunovion filed action in New Jersey District Court for patent infringement in January 2015. The District Court decided that claim 14 covered lurasidone, lurasidone’s (-) enantiomer (found in LATUDA®, the commercial product by Sunovion), as well as mixtures of (-) and (+) enantiomers, and issued a permanent injunction against the defendants from infringing the patent. The decision was timely appealed to the CAFC.
Decision
The question before the CAFC was what does claim 14 cover, i.e., whether it covered only the (-) enantiomer, or whether it covered only the racemic mixture. By way of background, the FDA approved drug contained lurasidone [or the (-) enantiomer] only as the active ingredient.
The defendants argued (as they did at the District Court) that the claim covered only a racemic mixture of the two enantiomers, and therefore, their proposed product containing only the (-) enantiomer would not be infringed by the filing of the ANDA and their proposed marketing of the generic version of the drug. The defendants’ argument centered mainly on the depiction of the structural formula of the racemic mixture as Compound No. 101 in the ’372 patent at col. 30, under Example 1(a), as reproduced below:
Since the structural formula depicted for the racemic mixture (Compound No. 101) is the same as the structural formula found in claim 14, the defendants contended, claim 14 should be construed to cover only the racemic mixture and not the pure (-) enantiomer only. Furthermore, the defendants pointed to the method of preparation of the (-) enantiomer in Example 1(e), which involves isolating the hydrochloride salt of the (-) enantiomer from the mother liquor left over after the removal of the (+) enantiomer from Compound No. 101. The defendants also pointed to the numbering of the (-) enantiomer hydrochloride with a different compound number, i.e., Compound No. 105 in Example 1-(e). Additionally, the defendants pointed to the specification providing optical rotation data for Compound No. 105 (but no optical rotation data was provided for Compound No. 101). The ’372 patent did not, however, provide a structural formula for Compound No. 105.
However, the CAFC decided that claim 14 covered at a minimum the enantiomer present in LATUDA, the commercial product, i.e., the (-) enantiomer, for the following reasons.
Both parties agreed that the structure depicted in the claim is the (-) enantiomer (based on plain language of the claim). Both parties agreed even when looked at in a vacuum, a Phosita would understand that the depicted structure would be one way of depicting the (-) enantiomer. There was also nothing in the specification or in the prosecution history to limit its scope to only the enantiomer mixture (racemate). The specification did not exclude the (-) enantiomer; rather, it said it is a preferred embodiment. Example 1(e) described a method of obtaining Compound 105, the (-)-enantiomer HCl, from Compound 101 (the racemic mixture) and also provided data on Compound 105 (m.p. 268 °C and optical rotation [α]25D= - 45.7 (c=1.0, methanol)) (cf. Compound 101 hydrochloride, m.p. 215-217 °C).
CAFC declined to decide whether the claim covered the other enantiomer or a mixture of enantiomers (as the District Court decided) since it was unnecessary to do so in this instance.
Circuit Judges Moore, Mayer, and Stoll constituted the panel, with J. Stoll writing the opinion with no dissent.
Practice Pointers
In order to avoid such claim construction issues, when patent applications are drafted, they should be drafted with more accurate description of the racemic mixtures and their enantiomers, either in properly delineating words or by specific structural formulas. Where it is not possible to add it to the specification, at least a more clearly worded claim should be included during prosecution of the application.
Some examples are provided below merely as a guideline for practitioners.
(1) Draft the patent application to include the more accurate structure of the (-)-enantiomer:
as submitted to the FDA in the NDA filed by Sunovion in the ’372 patent.
(2) Draft the patent application to include the full name of the enantiomer including R, S configuration:
(3aR,4S,7R,7aS)-2-(((1R,2R)-2-((4-(benzo[d]isothiazol-3-yl)piperazin-1-yl)methyl)cyclohexyl)methyl)hexahydro-1H-4,7-methanoisoindole-1,3(2H)-dione hydrochloride.
(3) If it is a racemic mixture, preferably use solid bonds (not wedges or dashed lines) and describe it as a racemic mixture.
(4) If it is a particular enantiomer that is desired, indicate the structure of the enantiomer by the use of wedges and dashed lines in all bonds (and in all stereo centers), not just some of the bonds as was done in the ‘372 patent; and also indicate whether it is a pure enantiomer. If the optical purity is known, or a particular optical purity is desired, indicate that also. For a good example, see the very detailed description of the R-trans enantiomers of the invention provided in U.S. Patent 4,681,893 and the specific structural formula representing the R-trans and S-trans enantiomers provided in claim 1 of the patent. Claim 1 was construed by the CAFC, in favor of the patentee, to cover the R-trans isomer used in the FDA approved product (Pfizer, Inc. v. Ranbaxy Labs., Ltd., 457 F.3d 1284 (Fed. Cir. 2006).
(5) Include a specifically crafted claim, e.g., stating it is “the (-) enantiomer of the desired compound”.
(6) Include a claim reciting structure and a property, e.g., optical rotation, melting point.
(7) Include a process claim for preparing or isolating the desired enantiomer and also a product obtained by the process claim.