Levothyroxine – USA

On Jul. 31, 2020, Federal Circuit affirmed district court’s decision which found levothyroxine composition patent invalid as indefinite under 35 U.S.C. § 112.

Background:

IBSA Institut Biochimique / IBSA Pharma Inc. (Plaintiffs) held NDA for Tirosint®(levothyroxine sodium) soft gel capsule.  Teva (Defendant) filed ANDA with USFDA to market generic version of Tirosint®.  Plaintiffs sued defendant for infringement of US 7,723,390 patent. The ’390 patent, entitled “Pharmaceutical Formulations for Thyroid Hormones,” provides pharmaceutical formulations based on thyroid hormones enabling a safe and stable oral administration for thyroid disorders. After trial, the district court held claims 1, 2, 4, and 7–9 invalid as indefinite.

Central issue is the parties’ dispute over the construction of “half-liquid,” which appears in independent claim 1.

1. A pharmaceutical composition comprising thyroid hormones or their sodium salts in the form of either: a) a soft elastic capsule consisting of a shell of gelatin material containing a liquid or half-liquid inner phase comprising said thyroid hormones or their salts in a range between 0.001 and 1% by weight of said inner phase, dissolved in gelatin and/or glycerol, and optionally ethanol, said liquid or half-liquid inner phase being in direct contact with said shell without any interposed layers, or b) a swallowable uniform soft-gel matrix comprising glycerol and said thyroid hormones or their salts in a range between 0.001 and 1% by weight of said matrix.

IBSA proposed that the term “half-liquid” should be construed to mean “semi-liquid, i.e., having a thick consistency between solid and liquid.” Teva argued that the term “half-liquid” is indefinite or should be construed as “a non-solid, non-paste, non-gel, non-slurry, nongas substance.”

Court’s analysis:

Federal Circuit first looked at the claim & said that the claim language of the ’390 patent does not make the meaning of “half-liquid” reasonably clear. The term “half-liquid” is merely used alongside “liquid” to describe the inner phase of a soft elastic capsule. Next looking at the specification, Federal Circuit said that the paragraphs in the specification designate a “half-liquid” is an alternative to the other members of the list, including pastes and gels which can be considered a phase between solid & liquid. Therefore, it is distinct from the “semi-liquid” as suggested by plaintiffs. Plaintiffs argued that priority (Italian) application is the best source to understand because the term “semiliquido” appears in the Italian Application as the same number of times, in the same places, to describe the same things” as “half-liquid” does in the ’390 patent. A POSA would therefore equate “semiliquido” with “half-liquid.” But Federal Circuit said that there are substantial differences between priority aplplication & ‘390 patent.  Therefore, POSA would likely consider the discrepant usage of “half-liquid” and “semiliquido” between the ’390 patent and the Italian Application to be intentional, implying that the different word choice has a different scope. In addition to the Italian Application, another portion of the prosecution history reinforces conclusion that the applicant intentionally used “half-liquid” instead of “semiliquid.” During the prosecution of the ’390 patent the applicant had a pending claim using “half-liquid” and another claim, depending from that claim, using the term “semi-liquid.” This is additional evidence that the applicant knew the term “semi-liquid” & “half-liquid” are mean to something different. Thus, the intrinsic evidence failed to establish the boundaries of a “half-liquid.”

Turning to the extrinsic evidence, Federal Circuit said that district court correctly held that dictionary definitions and four patents that predated the ’390 patent are not related to the ’390 patent and therefore do not provide context for what “half-liquid” means. In addition, the court found that Dr. Chyall was unable to articulate a boundary for what constitutes a “half-liquid” and could not tell how a skilled artisan would know when matter is not a “half-liquid” inner phase. Dr. Chyall was also unsure whether his construction of “half-liquid” would exclude the types of gel and slurry distinguished during prosecution.

Federal Circuit thus held that the intrinsic and extrinsic evidence failed to inform, with reasonable certainty, those skilled in the art about the scope of the invention. Therefore, claims are invalid as indefinite.