Hospira, Inc. v. Sandoz Inc.

August 16, 2012

GENERICally Speaking

Case Name: Hospira, Inc. v. Sandoz Inc., Civ. No. 09-4591 (MLC), 2012 U.S. Dist. LEXIS 63227 (D.N.J. May 4, 2012) (Cooper, J.) 

Drug Product and Patent(s)-in-Suit: Precedex® (dexmedetomidine hydrochloride); U.S. Pat. Nos. 4,910,214 ("the '214 patent") and 6,716,867 ("the '867 patent")

Nature of the Case and Issue(s) Presented:  The '214 and '867 patents are directed to the composition and use of dexmedetomidine hydrochloride.  In particular, the '214 patent claims the optical isomer of an imidazole derivative medetomidine, dexmedetomidine, and its use in a method of sedation/analgesia or treatment of anxiety or hypertension.  The l-enantiomer of medetomidine has little to no activity as compared to dexmedetomidine.  The '867 patent claims the use of dexmedetomidine for sedation in the intensive care unit.  Hospira filed suit against Sandoz's ANDA seeking to market a generic version of Precedex.  The parties stipulated that the ANDA product would infringe the asserted claims, should the claims be found valid and enforceable.  Only the issues of invalidity and unenforceability were tried to the Court.  The Court held that the '214 patent was valid, enforceable, and infringed by Sandoz.  The Court further held that the '867 patent was not anticipated, not unenforceable due to inequitable conduct, but was obvious and therefore invalid.   

Why Hospira Prevailed:  The Court first held that the "Savola Thesis" did not anticipate the '214 patent. The Savola Thesis describes the sedative and cardiovascular effects of medetomidine.  The reference specifically refers to medetomidine as being a racemic mixture and that it is a selective agonist "that would be interesting to study further."  Based on this last statement, however, the Court rejected Sandoz's §102 argument.  The phrase is insufficient to prove that the Savola Thesis discloses that medetomidine's resolution had actually taken place and suggests a future event.  The Court concluded that the Savola Thesis did not disclose the separated enantiomers; it only disclosed racemic medetomidine.  Next, the Court rejected Sandoz's obviousness argument.  The Court found that at the time of the invention there was considerable disagreement in the field regarding how difficult resolution of racemates might have been.  While the prior art would have motivated a person of ordinary skill in the art to separate medetomidine's enantiomers, there was not a reasonable expectation of success in doing so.  The Court's finding is based, in part, on the fact that Sandoz's expert could not recall having actually performed a resolution by 1987 and has, to this day, never performed a complete fractional crystallization by diastereomeric salts.  The Court also found that the evidence of unexpected results and commercial success contributed to a finding of non-obviousness.

Concerning the '867 patent, the Court first held that the "Talke" reference did not anticipate the asserted claims.  Talke studied the hemodynamic effects of perioperatively administered dexmedetomidine in a high-risk class of surgical patients, and reported on observations regarding sedation of the those patients.  The Court found, however, that Talke did not necessarily disclose that the patient received intensive care treatment.  While Sandoz proffered evidence that Talke likely disclosed continuing arousable sedation, and it likely disclosed use in an intensive care setting, such evidence was insufficient to demonstrate clearly and convincingly that the patent was invalid as anticipated.  But with respect to obviousness, the Court found that intravenous dexmedetomidine administration to intensive care patients would have been obvious to a person of ordinary skill at the time of the invention.  Any differences between the method of sedation in the '867 patent and the prior art "are insignificant such that giving those insignificant differences weight would result in an inflexible and rigid application of the obviousness test."  A person of ordinary skill would be motivated to use dexmedetomidine for sedation based on common sense inferences she would make in light of the prior art.  That no prior art disclosed clinical trials involving dexmedetomidine sedation in intensive care patients was not fatal to Sandoz's obviousness argument because "there is no requirement that a teaching in the prior art be scientifically tested, or even guarantee success, before providing a reason to combine" references.  Lastly, the Court found no evidence of secondary considerations of nonobviousness.  The law obligates a generic manufacturer to copy the branded product so any evidence of "copying" is less persuasive.  Hospira also did not submit any evidence that others tried and failed to develop an intensive care sedative.  And there was no evidence of commercial success because before the procedural indication was approved, Precedex did not meet Hospira's sales expectations.

Sandoz further argued that the patents-in-suit were unenforceable due to inequitable conduct.  It is undisputed that the Table 2 data in the '214 patent was "not only incorrect, but scientifically impossible."  Further, the Examiner relied on the Table 2 data and the applicant's argument based on that data to allow the '214 claims.  The correct data, which demonstrated that dexmedetomidine was twice as active as medetomidine rather than three times as active, was in an internal report within the same company that employed the '214 patent inventor.  Because of this, the Court found that Sandoz had satisfied the materiality standard.  In light of Therasense, however, the Court did not find the requisite "knowledge and deliberate action" on the part of the inventor to deceive the Patent Office.  There was no evidence that the inventor ever saw the corrected data and he could not recall whether he or anyone else submitted the data to the company's patent department.  While frustrating, the inventor's lack of memory "cannot be used to demonstrate specific intent to deceive," and Sandoz could not meet its burden.

Sandoz's inequitable conduct defense with respect to the '867 patent is based on that inventor's failure to disclose the Talke reference to the Patent Office during prosecution.  The Court found that the Talke reference met the but-for materiality standard, in large part, based on its analysis earlier concerning anticipation/obviousness.  But the Court further found the inventor's explanation on why Talke was not presented to the Patent Office credible.  Throughout his testimony, the inventor repeatedly referred to and described Talke as a study focused on hemodynamic outcomes rather than sedation.  The Court held, therefore, that the inventor had a genuine belief that Talke did not need to be disclosed to the Patent Office, and that specific intent to deceive was not the single-most reasonable inference to be drawn from the inventor's actions.

As a result of the Court's finding that the '214 patent was valid, enforceable, and infringed, the Court entered a permanent injunction against Sandoz's commercial manufacture of its ANDA product until the expiration of the '214 patent.

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