Endo Pharmaceutical Solutions, Inc., Bayer et al. v. Custopharm Inc.

Docket No. 2017-1719

July 13, 2018

Brief summary: DC decision that Endo’s/Bayer’s claims relating to Endo’s Aveen® were not proven invalid for obviousness affirmed (e.g., the prior art did “not inherently disclose benzyl benzoate as a co-solvent or the particular ratio”).

Summary: Custopharm appealed DC concluding that Endo’s/Bayer’s claims of US 7,718,640 and 8,338,395 relating to Endo’s testosterone undecanoate (TU) intramuscular injection (Aveen®) were not proven invalid for obviousness (§ 103). Custopharm filed a paragraph IV-based ANDA and Endo/Bayer sued for infringement of the ‘640 and ‘395 patents. The FC panel opinion explains that “[t]he key elements of [the] claims in dispute are: (1) 750 mg TU, (2) vehicle consisting of castor oil and a co-solvent (benzyl-benzoate in the ‘640 patent), and (3) an injection schedule comprising two initial injections at an interval of four weeks followed by injections at ten week intervals (‘395 patent only).” Castopharm alleged invalidity for obviousness in view of the “Behre”, “Nieschlag”, and “von Eckardstein” references (“the Articles”) that “describe small clinical studies involving 1000 mg TU injections” and “using a composition of 250 mg/ml TU in castor oil” but “do not disclose or describe the use of a co-solvent.” The FC panel noted that “[w]hile the actual formulation of the vehicle used in the studies was 40% castor oil and 60% benzyl benzoate, this was not reported and thus unknown to a skilled artisan until 2007, years after the 2003 priority date for the patents-in-suit (by the “Saad” reference). Custopharm also argued that the “Pushpalatha” and “Riffkin” references describe “an injectable composition of hydroxyprogesterone in a mixture of 40% castor oil and 60% benzyl benzoate” for administration “once a week to pregnant women to prevent miscarriage” and “the use of castor oil for the parenteral administration of steroids” (the product Proluton) and “a castor oil and benzyl benzoate vehicle to improve the solvent abilities of castor oil”, respectively. The DC concluded “that the Articles do not inherently disclose benzyl benzoate as a co-solvent or the particular ratio of solvent to co-solvent claims by the patents-in-suit simply because this formulation was what had been used in the studies forming the basis of the Articles”, citing Par Pharm. (FC 2014) and Continental Can (FC 1991) (“inherency may only supply a missing claim limitation if the limitation at issue is the ‘natural result’ of the combination of prior art elements of a ‘necessarily present’ limitation”). The DC also concluded that “the prior art did not disclose the specific injection schedule claimed in the ‘395 patent.” The FC panel found no clear error in the [DC’s] underlying factual findings” because, e.g., “Custopharm needed to affirmatively demonstrate that a skilled artisan would have been motivated to lower the dose of TU despite no clear evidence of overdosing under the FDA Guidelines” (Pfizer, FC 2007)). On inherency, the FC panel explained that “it is Custopharm’s burden to present clear and convincing evidence that the Articles necessarily disclosed the vehicle formulation” and that its evidence “fall short of meeting this burden” (Motorola, FC 2013) (e.g., Endo’s expert testified that “a skilled artisan would not have recognized that a co-solvent was necessary”) and the cases it cited “are inapposite” (e.g, In re Omeprazole, FC 2007 (“separating layer was, in fact, a natural result”); In re Crish, FC 2004 (nucleotide sequence inherently anticipated); “the Articles failed to disclose…benzyl benzoate, let alone the ratio”)). The FC panel also found no error with the DC’s conclusion of no motivation to combine with Proluton and Riffkin “they do not suggest that the co-solvent necessarily be benzyl benzoate as opposed to other co-solvents” and it was not shown “that a skilled artisan would have turned to the vehicle in Proluton when formulating a long-acting, injectable testosterone therapy.” Regarding the dosing schedule, the FC panel found no error with the DC’s conclusion that Custopharm did not show “that a skilled artisan would combine the lowered dose with the injection schedule in the manner claimed.” Thus, the DC decision was affirmed.

This entry was posted in Anticipation (35 USC 102), Generics / ANDA, Inherency, Obviousness. Bookmark the permalink.

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