Millenium Pharmaceuticals, Inc. v. Sandoz Inc. et al.


Docket No. 2015-2066 (several others)

NEWMAN, MAYER, O’MALLEY
July 17, 2017

Brief summary: DC decision that claims related to Millenium’s Velcade® are invalid for obviousness vacated and remanded.

Summary: Millenium appealed DC decision that claims 20, 31, 49 and 53 of US 6,713,446 relating to Velcade® (for treatment of multiple myeloma and mantel cell lymphoma) are invalid. Sandoz and several other parties filed ANDAs, and Millenium filed suit in DE. The ‘446 patent relates to the discovery that mannitol and the bortezomib formed an ester during lyophilization (Velcade®) and that it could act as a prodrug. The FC opinion explains that Velcade® followed many failed attempts to produce a stable liquid formulation and, citing Millenium’s brief, “became ‘a cancer treatment that changed the decades-old standard of care for multiple myeloma and has saved thousands of lives” approved by the FDA “in record time, despite its novel structure and mechanism of action.” The DC “held that the claims were obvious because they were the inherent result of an allegedly obvious process” (“an obvious option ‘from which the prior art did not teach away’…the Adams Patent ‘pointed directly to mannitol’”; relying in part on Sandoz’s witness testimony; Par Pharm., FC 2014). The DC also “found that Millenium did not establish unexpected results because it did not compare the claimed invention to a glycerol ester of bortezomib” and rejected its arguments regarding a long-felt need because the ester “did not solve any problem having persisted over a long period of time without resolution by the prior art.” After reviewing the DC’s factual findings for clear error and its determination of obviousness de novo (Allergan, FC 2003; Microsoft, US 2011 and In re Cyclobenzaprine, FC 2012 (“plenary review” regarding whether “the evidence satisfies the clear-and-convincing standard”)), the FC panel disagreed with the DC’s conclusion. It concluded, even though “mannitol was a known bulking agent, and lyophilization was a known method of drug formulation”, the ester is a “new compound with distinct chemical properties” that was not taught or suggested by the prior art and “Sandoz identifies no reference or combination of references that shows or suggests a reason to make the claimed compound” (Otsuka, FC 2012; Bristol-Myers, FC 2014; In re Rosuvastatin, FC 2012; Par Pharm., FC 2014; Pfizer, FC 2007). Further, the FC panel explained “[n]o reference teaches or suggests that such a new compound would have the long-sought properties of stability and solubility, and sufficiently dissociate to release bortezomib at an effective rate in the bloodstream, all critical to effective use for treating multiple myeloma.” It concluded the Adams Patent neither mentioned mannitol nor tought or suggested “the esters provide a solution to the problems of instability and insolubility of bortezomib” (“[N]either the requisite motivation nor expectation of success is found in the prior art…Sandoz provides no reason why a person of ordinary skill who is seeking to make esters of bortezomib would look to lyophilization bulking agents.”) The FC panel also found the DC erred in teaching away analysis since, e.g., “Millenium offered persuasive evidence that the chemical modification of bortezomib would have been unattractive” (In re Urbanski, FC 2016 (skilled artisan “would be discouraged…or led in a [divergent] direction”)). It found the DC’s consideration of inherency (Par Pharm.; In re Oelrich, CCPA 1939) to be flawed as well since, e.g., “[t]he mere fact that a certain thing may result from a given set of circumstances in not sufficient’ to render the result inherent” (In re Oelrich, CCPA 1939; Par Pharm.), “invention is not a matter of what the inventor intended when the experiment was performed”, and “[t]he inventor’s own part itself never leads to a conclusion of obviousness; that is hindsight” (Otsuka; In re Kratz, CCPA 1979; Life Techs., FC 2000)). The FC panel also found error in the DC’s consideration of the Millenium’s evidence of unexpected results (“unexpectedly superior stability, solubility, and dissolution”) and a long-felt need (DC “conclusion…was both perfunctory and clearly erroneous” since, e.g., “bortezomib alone…is not a viable commercial product” and “[t]he D-mannitol ester was responsible for Velcade®’s successful results”) (Leo Pharm., FC 2013 (“objective indicia enable ‘the court to avert the trap of hindsight’…Unexpected results are useful to show the improved properties by the claimed compositions are much greater than would have been predicted.”)). The DC decision was therefore vacated and remaned, as was litigation with Apotex and Teva.

This entry was posted in Generics / ANDA, Obviousness, Obviousness-Teaching Away. Bookmark the permalink.

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