By Thomas Long, J.D.
A generic version of the drug Sensipar®—used for the treatment of secondary hyperparathyroidism—for which pharmaceutical company Zydus sought approval—would infringe various asserted claims of a patent held by brand-name drug maker Amgen Inc., the federal district court in Wilmington, Delaware, has decided after a bench trial. The court sided with Amgen’s argument that the proposed Zydus generic contained a component that was classified as a diluent, rather than a binder, meaning that it could not escape being covered by the asserted claim limitations. Zydus’s counterclaims for invalidity will be considered separately. Three other proposed generic versions of the drug—by Amneal, Watson, and Piramal—did not infringe the patent because they contained binders that were not listed in the patent claims and were not equivalents to the listed binders (Amgen Inc. v. Amneal Pharmaceuticals LLC, July 27, 2018, Goldberg, M.).
Patent-in-suit. Amgen held U.S. Patent No. 9,375,405 ("the ’405 patent"), titled "Rapid Dissolution Formulation of Calcium Receptor-Active Compound." The ’405 patent was listed in the Orange Book as covering the brand-name drug Sensipar®. Amgen accused multiple companies of infringing the ’405 patent by filing Abbreviated New Drug Applications (ANDAs) seeking FDA approval to make and sell generic versions of Sensipar®.
Claim limitations. For most of the asserted claims, the parties stipulated that a finding of infringement would depend on the findings for claim 1 of the ’405 patent. Claim 1 recited a pharmaceutical composition combining specific excipients in specific amounts with the active ingredient cinacalcet hydrochloride ("cinacalcet HCI"). Excipients were the inert ingredients used in drug formulations to perform specific functions, such as diluent, binder, or disintegrant. Diluents provide bulk to the formulation so that the tablets are of sufficient size for handling. Binders act as the adhesive that holds the drug and excipients together. Disintegrants ensure the breakup of the tablet upon ingestion thereby promoting absorption of the drug substance. The parties’ stipulation did not cover three of the dependent claims Amgen asserted against various defendants, claims 5, 6, and 18. Claim 5 recited, "The composition according to claim 1, wherein the at least one binder is povidone." Claim 6 recited, "The composition according to claim 1, wherein the at least one disintegrant is crospovidone." Claim 18 recited, "The composition according to claim 1, wherein the hyperparathyroidism is primary hyperparathyroidism or secondary hyperparathyroidism."
Infringement allegations, trial. Defendants Amneal Pharmaceuticals LLC and Amneal Pharmaceuticals of New York LLC ("Amneal"); Watson Laboratories, Inc., Actavis, Inc., and Actavis Pharma, Inc. ("Watson"); Piramal Healthcare UK Ltd. ("Piramal"); and Zydus Pharmaceuticals (USA) Inc. and Cadila Healthcare Ltd. (d.b.a. Zydus Cadila) ("Zydus") all separately sought approval to market a generic version of cinacalcet hydrochloride in 30, 60, and 90 mg dosage strengths. Amgen asserted that the proposed products will infringe claims 1-4, 6, 8-9, and 15-20 of the ’405 patent. The separate lawsuits were consolidated, and the court bifurcated the infringement claims and the defendants’ invalidity counterclaims for trial. The court held a four-day bench trial on infringement.
Infringement—Amneal. To prove infringement by Amneal, Amgen had the burden to show by a preponderance of the evidence that Amneal’s binder Opadry was either a listed member of the "Markush group" of binders in the asserted patent claims (that is, the list of alternative binders that could be selected for the claimed composition) or equivalent to a listed member. Amgen did neither, the court said. Claim 1 of the ’405 patent did not list Opadry in the Markush group for binders, and Amgen failed to prove that Opadry was a pseudonym for the listed binder hydroxypropyl methylcellulose. The evidence established that Opadry’s binding mechanism was different from the listed binders. In addition, Amneal’s accused product included an unlisted disintegrant (pregelatinized starch) that functioned as a disintegrant. Thus, according to the court, Amgen failed to show by a preponderance of the evidence that Amneal’s accused product infringed the binder and disintegrant limitations of the ’405 patent. Amneal therefore did not infringe claim 1 of the ’405 patent. That meant, pursuant to the parties’ stipulation, Amneal did not infringe claims 2-4, 8-12, and 14-17. The court also concluded that Amgen did not prove by a preponderance of the evidence that Amneal infringed dependent claims 6 and 18, because one who does not infringe an independent claim cannot infringe the dependent claims.
Infringement—Watson. The parties disputed whether Watson’s ANDA product infringed the binder and disintegrant limitations of claim 1. The court said that it was not necessary to address the binder limitation, however, because a finding of noninfringement could be based on the disintegrant limitation alone. Amgen failed to show that the disintegrant in Watson’s generic product infringed claim 1 under the doctrine of equivalence via either the "function-way-result" test or the "insubstantial differences" test. Therefore, Watson did not infringe claim 1 of the ’405 patent, and per the parties’ stipulation, Watson did not infringe claims 2-4, 8-17, and 19-20. The court also determined that Watson did not infringe claims 5, 6, and 18.
Infringement—Piramal. Similarly to Watson’s ANDA product, the court found that a finding of noninfringement regarding Piramal’s product could be made solely on the binder limitation. Amgen argued that the binder in Piramal’s ANDA product—pregelatinized starch—was equivalent to povidone, a binder in Amgen’s Markush list. However, the court decided that Amgen was precluded by prosecution history estoppel from making this assertion. To overcome an obviousness objection during prosecution, Amgen accepted a narrowing amendment to the claim such that Amgen surrendered all equivalents in "the territory between the original claim and the amended claim." Amgen was able to overcome the prior art by claiming a smaller set of the binders disclosed in the prior art, the court explained. By agreeing to the claim amendment, Amgen abandoned the other binders disclosed in the prior art—which included pregelatinized starch. Therefore, Amgen’s infringement contentions against Piramal failed.
Infringement—Zydus. The Zydus product also contained pregelatinized starch. However, with respect to this product, Amgen took the position that it functioned as a diluent, as stated in Zydus’s ANDA, whereas Zydus took the position that it functioned as a binder. Zydus’s position adopted an opinion that Amgen’s expert asserted against other defendants; therefore, the court noted, Amgen could prevail on its infringement theory only if its own expert’s opinion was unpersuasive. The court found that Amgen did not prove by a preponderance of the evidence that pregelatinized starch should be artificially divided into two fractions, with each fraction alone serving a different function. As a result, Zydus was unable to defeat Amgen’s assertions of literal infringement by adopting Amgen’s expert’s opinion that the cold water soluble fraction of pregelatinized starch functioned as a binder. The court therefore concluded that Zydus’s ANDA product literally infringed claim 1 to the extent the claim was found valid and enforceable. Pursuant to the stipulation, Zydus also would infringe claims 2-4, 8-9, 15-17, and 19. The court also found that the product infringed claim 6, but because Amgen did not present argument on claims 18 and 20, it did not carry its burden with respect to the latter two claims.
The case is No. 1:16-cv-00853-MSG.
Attorneys: Jack B. Blumenfeld (Morris, Nichols, Arsht & Tunnell LLP) for Amgen Inc. David Ellis Moore (Potter Anderson & Corroon, LLP) for Amneal Pharmaceuticals LLC and Amneal Pharmaceuticals of New York LLC. John W. Shaw (Shaw Keller LLP) for Watson Laboratories, Inc., Actavis, Inc., and Actavis Pharma, Inc. John C. Phillips, Jr. (Phillips, Goldman, McLaughlin & Hall, P.A.) for Piramal Healthcare UK Ltd., Zydus Pharmaceuticals [USA] Inc., and Cadila Healthcare Ltd. [d.b.a. Zydus Cadila].
Companies: Amgen Inc.; Amneal Pharmaceuticals LLC; Amneal Pharmaceuticals of New York LLC; Watson Laboratories, Inc.; Actavis, Inc.; Actavis Pharma, Inc.; Piramal Healthcare UK Ltd.; Zydus Pharmaceuticals [USA] Inc.; Cadila Healthcare Ltd. [d.b.a. Zydus Cadila]
MainStory: TopStory Patent DelawareNews
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