Bristol-Myers Squibb Company v. Teva Pharmaceuticals USA, Inc. (2nd UPDATE)

Bristol-Myers Squibb Company v. Teva Pharmaceuticals USA, Inc., petition for rehearing en banc (denied)
October 20, 2014

Request for certiorari denied May 6, 2015 (14-886)

Summary: Bristol-Myers’ petition for rehearing en banc of the finding that claim 8 of its US 5,206,244 encompassing the hepatitis B drug entecavir (marketed as Baraclude®) would have been obvious (decided June 12, 2014) was denied. The original decision turned in part on whether post-filing evidence that the prior art compound 2′-CDG was toxic in vivo was persuasive evidence of non-obviousness. The concurring and dissenting opinions in this denial offer interesting perspectives on the obviousness analysis in general and whether this case should have been considered en banc. Judges Dyk and Wallach concurred because while “[t]he patent applicant’s discovery of unexpected results at the time of the invention can help establish that the invention would not have been obvious…hindsight bias must be avoided…under longstanding Supreme Court authority, the pertinent knowledge is that possessed at the time of the invention” (KSR, US 2007, at 416). Judge O’Malley also concurred, explaining that the decision does not “close[] the door to all” later-discovered unexpected results (Glenmark, FC 2014; Genetics Inst., FC 2011; Knoll Pharm., FC 2004) and that in fact “post-issuance evidence regarding objective indicia of non-obviousness may often be the most probative and cogent evidence on the record” (Stratoflex, FC 1983). Here, Judge O’Malley writes, the DC simply found “that the later evidence of 2’-CDG’s toxicity was insufficient to overcome the strong evidence that researchers at the time had a motivation to start with 2’-CDG as the lead compound and modify it in such a way as to make entecavir” (“the results upon which BMS relied were not truly unexpected or substantial”). Judges Newman, Lourie and Reyna dissented, describing the decision as hindsight and “ignoring the unexpected differences in properties” (also citing Genetics Inst., FC 2011; Knoll, FC 2004 (“no requirement that an invention’s properties and advantages were fully known before the patent application was filed, or that the patent application contains all of the work done in studying the invention”); and Glenmark, FC 2014 (“patentability may consider all of the characteristics possessed by the invention, whenever those characteristics become manifest”)). They also pointed to cases relating to “[c]omparisons of newly found properties of both the invention and the prior art” including Leo Pharm., (FC 2013) (degradation of prior art vitamin D formulations), In re Payne (CCPA, 1979) (comparison of pesticides), In re Khelghatian (CCPA, 1966) (evidence in a Rule 132 declaration), and In re Miller (CCPA 1952) (“comparative tests and the establishment of unexpected and superior results never before attained”). This dissent also argued that while “[t]he court stated that ‘unexpected results do not per se defeat, or prevent, the finding of a modification to a lead compound will yield expected, beneficial properties…an unexpected result or property is the touchstone of nonobviousness” (citing In re Soni, FC 1995; Procter & Gamble (FC 2009); and several other cases). This dissent also wrote the the court’s holding “that a ‘mere difference in degree’ is ‘insufficient’ to render a compound unpatentable’” was flawed, especially “here, where the court held that a new and effective non-toxic treatment for hepatitis B is merely a difference in degree from a highly toxic and useless treatment for hepatitis B” (citing In re Wagner, CCPA 1967; In re Chupp (CCPA 1967) (five times greater crop safety over prior art compounds); In re Weichert (CCPA 1967) (“it is possible to obtain a patent where the showing proves substantially greater effectiveness”)). Judges Taranto, Lourie and Reyna also dissented because “the panel decision seems highly likely to be viewed as addressing the timing-of-evidence question…[a]nd that question is worthy of further attention” (“statements in opinions must be read in context, considering their role in the decision and the facts of the case…advocates often ignore that principle…the panel opinion should not be taken to stand for certain propositions for which advocates are likely to cite it.”) For example, this dissent discussed that while In re Dillon (FC 1990) was cited to “explain[] that an unexpected result or property does not by itself support a finding of nonobviousness”, “the PTO properly found no unexpected results” (as the panel found in this case) and this point could be missed. It also suggested another question raised by this case is whether in vitro data could provide a reasonable expectation of success in using the drug in vivo as of the filing date (whether an expectation that 2’-CDG would have been safe in humans given it had only been tested in vitro “when Bristol-Myers filed for its patent”). In footnote 5, this dissent quotes several references explaining that in vitro tests are not generally reliable indicators of in vivo results (“[o]ptimism about the compound is not the same as a reasonably grouded prediction”). This dissent argued that this case should be heard en banc because many of these issues need to be clarified, for instance: “Should a reasonable expectation of success mean a mere educated guess or surmise of plausible possibility? Should it mean an affirmative well-grounded prediction, using a 50% or other probability, based on the standards that scientists would use professionally to assert such predictions…?”

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