Takeda Pharma. Co., Ltd. v. Zydus Pharma. USA Inc.

Case Name: Takeda Pharma. Co., Ltd. v. Zydus Pharma. USA Inc., Civ. No. 10-cv-1723 (JAP) (D.N.J. May 7, 2013) (Pisano, J.)

Drug Product and Patent(s)-in-Suit: Prevacid^® SoluTab (lansoprazole); U.S. Patent No. 6,328,994 (“the ’994 patent”) 

Nature of the Case and Issue(s) Presented: Only claim 1 of the ’994 patent remained at issue in this case. According to the patent specification, the fine granules in the formulation have an average particle diameter of about 400 µm or less. The ’994 patent claims enteric-coated drug granules to achieve the delayed-release of the drug into the intestine while passing through the stomach. A four-day bench trial was held concerning the issues of infringement and invalidity. Takeda contended that Zydus infringed the claim limitation of claim 1 related to the average particle diameter of the claimed granules. Zydus raised arguments concerning Section 112 defenses. The court ruled in favor of Takeda on all issues.

Why Takeda Prevailed: The court’s infringement analysis hinged on its claim construction of the term “fine granules having an average particle diameter of 400 µm or less” to mean “fine granules up to and including the enteric coating layer having an average particle diameter of 400 µm (+10%) or less.” Based on this construction, the upper limit of the “fine granules” within claim 1 is 440 µm. The focus of the infringement portion of the trial was the parties’ disagreement as to whether individual coated granules in Zydus’ ANDA product that are stuck together (i.e., agglomerates) should be de-agglomerated into their component, individual coated entities and counted as separate granules for purpose of determining average particle diameter of Zydus’ “fine granules.” The specification describe “fine granules” as comprising a “single core,” and both parties’ experts agreed that the goal of pharmaceutical manufacturing is to generate individual coated granules, not agglomerates. Therefore, a person of ordinary skill (POSA) would know to de-agglomerate particles before measuring particle size. For three samples, Takeda’s expert obtained measurements that were less than 440 µm, thus, Zydus’ ANDA product was covered by the ’994 patent.

Zydus next contends that claim 1 of the ’994 patent is invalid under 35 U.S.C. § 112 for lack of enablement because it alleges that there are certain methodologies for the determination of average particle diameter that cannot be used without undue experimentation. Specifically, Zydus argues that a POSA would not know what Coulter counter instrument parameters and sample preparation techniques to apply when measuring the particle size of fine granules. But Zydus did not offer any more specific evidence of the amount of experimentation necessary to use a Coulter counter instrument or of past failed efforts to use that instrument to measure the particle size. Takeda’s expert also testified that it is well within the ability of POSA to carry out these experiments and instrument companies are trying to make that process “turn-key.” The court noted that Zydus itself used the ’994 patent to measure particle size using laser diffraction without undue experimentation.

Zydus also contends that claim 1 is invalid for lack of enablement because different particle size measurement methodologies produce different particle size results in relation to the same sample. But Zydus’ theory “is based on the incorrect assumption that there is only one ‘correct’ average particle diameter for any given unknown sample that can only be measured by one particle size measurement technique.” A POSA would know that there is no single correct particle size. Zydus’ expert agreed that different particle size results produced different measurements, yet all are equally correct.

Zydus contends that the court’s claim construction, incorporating a 10% deviation, renders the ’994 patent invalid under 35 U.S.C. § 101 and § 112 for lack of enablement because it captures inoperative species—particles greater than a maximum particle size and large, conventional particles. The ’994 patent refers to a “maximum particle size” that is “practically 425 µm or less.” But the patent treats the maximum particle size and the median particle diameter as two separate and distinct concepts. Claim 1 does not include a maximum particle size limitation; claim 7 does. The ’994 patent also distinguishes the “fine granules” and “conventional granules” concepts. The ’994 patent describes “fine granules” as having “an average particle diameter of about 400 µm or less in order that roughness is not felt in the mouth.” Thus, a POSA would understand that conventional granules, defined as producing a rough feeling in the mouth, to be 440 µm or greater.

Zydus offered other Section 112 arguments concerning lack of written description and non-enablement, but was not able to meet its burden in showing (i) that a POSA would not know how to extract granules from a finished tablet prior to subjecting those granules to particle size testing; (ii) that compression forces would impact particle size.

Finally, Zydus’ indefiniteness argument was also rejected. Zydus argues that when the + 10% variance is applied to the “400 µm or less” term, the upper limit is somewhere between 440 and 360 µm, and that is an indefinite upper limit. The court found that a POSA recognizes that the “minus 10%” or “360 µm” limit is immaterial because it is already encompassed by the “plus 10%” or “440 µm” limit.